Q29982	Involved in susceptibility to Stevens-Johnson syndrome [MIM:608579]. This is a life-threatening reaction of the skin to particular types of medication. It is characterized by high fever, malaise and blistering exanthema. The more severe form of the disease is referred to as toxic epidermal necrolysis.
Q29846	HLA-B27 is associated with the development of ankylosing spondylitis (AS) [MIM:106300]. AS is a chronic inflammatory rheumatic disease that mainly affects the axial skeleton and is considered the prototype of seronegative spondyloarthropathies (SNSA), which include reactive arthritis (e.g., Reiter's syndrome), psoritic spondylitis, and other spondyloarthropathies (SpA). In the Greek Cypriot population, a restricted number of HLA-B27 subtypes are associated with AS and other B27-related diseases and an elevated frequency of the B*2702 allele in the AS patients is identified. The allele B*2707 seems to have a protective role in this population because it was found only in the healthy controls.
Q29963	Genetic variation in HLA-C is associated with susceptibility to psoriasis 1 (PSORS1) [MIM:177900]. Psoriasis is a chronic inflammatory dermatosis that affects approximately 2% of the population. It is characterized by red, scaly skin lesions that are usually found on the scalp, elbows, and knees, and may be associated with severe arthritis. The lesions are caused by hyperproliferative keratinocytes and infiltration of inflammatory cells into the dermis and epidermis. The usual age of onset of psoriasis is between 15 and 30 years, although it can present at any age.
Q00005	Defects in PPP2R2B are the cause of spinocerebellar ataxia type 12 (SCA12) [MIM:604326]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA12 is an autosomal dominant cerebellar ataxia (ADCA).
Q5Y7E9	Allelic variation at the HLA-DRB1 locus is a major contributor to genetic predisposition for sarcoidosis [MIM:181000]. Sarcoidosis is a disease of unknown etiology in which there are chronic inflammatory granulomatous lesions in lymph nodes and other organs.
P01903	Genetic variations in HLA-DRA are associated with susceptibility to hepatitis B virus infection (HBV infection) [MIM:610424]. Approximately one third of all cases of cirrhosis and half of all cases of hepatocellular carcinoma can be attributed to chronic HBV infection. HBV infection may result in subclinical or asymptomatic infection, acute self-limited hepatitis, or fulminant hepatitis requiring liver transplantation.
P26439	Defects in HSD3B2 are the cause of adrenal hyperplasia type 2 (AH2) [MIM:201810]. AH2 is a form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late onset (NC or LOAH), and 'cryptic' (asymptomatic). In AH2, virilization is much less marked or does not occur. AH2 is frequently lethal in early life.
P26439	Mild HSD3B2 deficiency in hyperandrogenic females is associated with characteristic traits of polycystic ovary syndrome, such as insulin resistance and luteinizing hormon hypersecretion.
Q9H2F3	Defects in HSD3B7 are the cause of congenital bile acid synthesis defect type 1 (CBAS1) [MIM:607765]; also known as neonatal progressive intrahepatic cholestasis. CBAS1 is due to a primary defect in bile synthesis leading to progressive liver disease. Clinical features include neonatal jaundice, severe intrahepatic cholestasis and cirrhosis.
P78314	Defects in SH3BP2 are the cause of cherubism (CRBM) [MIM:118400]. CRBM is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws, which often begins around three years of age. It is followed by development of fibrous tissue masses, which causes a characteristic facial swelling.
Q9Y578	Defects in EPB41 are the cause of elliptocytosis type 1 (EL1) [MIM:611804]. EL1 is a Rhesus-linked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant, hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.
Q9Y578	Defects in EPB41 are a cause of hereditary pyropoikilocytosis (HPP) [MIM:266140]. HPP is an autosomal recessive hematologic disorder characterized by hemolytic anemia, microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of red cells.
Q9UC43	Defects in NT5C3 are the cause of P5N deficiency (P5ND) [MIM:266120]; also called hemolytic anemia due to P5N deficiency or hemolytic anemia due to UMPH1 deficiency. P5ND is an autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stipplig and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties.
Q676U5	Genetic variations in ATG16L1 are associated with susceptibility to inflammatory bowel disease type 10 (IBD10) [MIM:611081]. IBD is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease (CD) and ulcerative colitis phenotypes. IBD10 individuals show the phenotype characteristic to CD. It may involve any part of the gastrointestinal tract, but most frequently the terminal ileum and colon. CD is commonly classified as autoimmune disease.
P08697	Defects in SERPINF2 are the cause of alpha-2-plasmin inhibitor deficiency (APLID) [MIM:262850]. APLID is an autosomal recessive disorder resulting in severe hemorrhagic diathesis.
Q9UCB6	Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:104300]. AD1 is a familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C- terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.
Q9UCB6	Defects in APP are the cause of amyloidosis cerebroarterial Dutch type (AMYLCAD) [MIM:605714]; also known as hereditary cerebral hemorrhage with amyloidosis Dutch type (HCHWAD). AMYLCAD is a hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. Beta-APP40 is the predominant form of cerebrovascular amyloid. Amyloid is not found outside the nervous system. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Onset of the disease is in middle age (44 to 60 years). Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease.
Q9UCB6	Defects in APP are the cause of amyloidosis cerebroarterial Italian type (AMYLCAIT) [MIM:605714]. AMYLCAIT is a hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels, resulting in cerebral amyloid angiopathy. Amyloid is not found outside the nervous system. It is a condition very similar to AMYLCAD, but the clinical course is less severe. Patients manifest mild cognitive decline, recurrent strokes, and epilepsy in some cases. There are extensive amyloid deposits in leptomeningeal and cortical vessels and, to a lesser extent, in the neuropil of the cerebral cortex, in the absence of neurofibrillary tangles.
Q9UCB6	Defects in APP are the cause of amyloidosis cerebroarterial Iowa type (AMYLCAIW) [MIM:605714]. AMYLCAIW is a hereditary amyloidosis due to amyloid-beta A4 peptide(s) deposition. Patients have progressive aphasic dementia, leukoencephalopathy, and occipital calcifications.
Q9NRG9	Defects in AAAS are the cause of achalasia-addisonianism- alacrima syndrome (AAAS) [MIM:231550]; also known as triple-A syndrome or Allgrove syndrome. AAAS is an autosomal recessive disorder characterized by adreno-corticotropic hormone (ACTH)- resistant adrenal failure, achalasia of the esophageal cardia and alacrima. The syndrome is associated with variable and progressive neurological impairment involving the central, peripheral, and autonomic nervous system. Other features such as palmoplantar hyperkeratosis, short stature, facial dysmorphy and osteoporosis may also be present.
Q6NSC9	Defects in SERPINA3 may be a cause of chronic obstructive pulmonary disease (COPD) [MIM:107280].
Q9UGJ0	Defects in PRKAG2 are the cause of Wolff-Parkinson-White syndrome (WPWS) [MIM:194200]; also known as preexcitation syndrome. It is the second most common cause of paroxysmal supraventricular tachycardia.
Q9UGJ0	Defects in PRKAG2 are a cause of cardiomyopathy familial hypertrophic with Wolff-Parkinson-White syndrome (CHMWPWS) [MIM:600858]. HCM due to PRKAG2 mutations is probably due to polysaccharide storage in the heart. Defects in PRKAG2 may not be a frequent cause of HCM where no features of pre-excitation are found in affected individuals.
Q9UGJ0	Defects in PRKAG2 are a cause of glycogen storage disease of heart lethal congenital (GSDH) [MIM:261740]; also known as phosphorylase kinase deficiency of heart or congenital nonlysosomal cardiac glycogenosis. GSDH is a rare disease which leads to death within a few weeks to a few months after birth, through heart failure and respiratory compromise.
Q9MYP4	Defects in PRKAG3 are the cause of the RN- phenotype which is associated with excess glycogen content (about 70%) in skeletal muscle. This mutation originated in the hampshire breed pigs and has beneficial effects on meat content but detrimental effects on processing yield. Thus, this mutation is of considerable economic significance in the pig breeding industry.
Q9UDR5	Defects in AASS are the cause of hyperlysinemia [MIM:238700]. Hyperlysinemia is an autosomal recessive condition characterized by hyperlysinemia lysinuria and variable saccharopinuria.
Q9UN09	Defects in ABCA1 are a cause of high density lipoprotein deficiency type 1 (HDLD1) [MIM:205400]; also known as analphalipoproteinemia or Tangier disease (TGD). HDLD1 is a recessive disorder characterized by absence of high density lipoprotein (HDL) cholesterol from plasma, accumulation of cholesteryl esters, premature coronary artery disease (CAD), hepatosplenomegaly, recurrent peripheral neuropathy and progressive muscle wasting and weakness.
Q9UN09	Defects in ABCA1 are a cause of high density lipoprotein deficiency type 2 (HDLD2) [MIM:604091]; also known as familial hypoalphalipoproteinemia (FHA). HDLD2 is inherited as autosomal dominant trait. It is characterized by moderately low HDL cholesterol, predilection toward premature coronary artery disease (CAD) and a reduction in cellular cholesterol efflux.
Q99758	Defects in ABCA3 are the cause of pulmonary surfactant metabolism dysfunction type 3 (SMDP3) [MIM:610921]; also called pulmonary alveolar proteinosis due to ABCA3 deficiency. A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.
P78363	Defects in ABCA4 are the cause of Stargardt disease type 1 (STGD1) [MIM:248200]. STGD is one of the most frequent causes of macular degeneration in childhood. It is characterized by macular dystrophy with juvenile-onset, rapidly progressive course, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material. STGD1 inheritance is autosomal recessive.
P78363	Defects in ABCA4 are the cause of fundus flavimaculatus (FFM) [MIM:248200]. FFM is an autosomal recessive retinal disorder very similar to Stargardt disease. In contrast to Stargardt disease, FFM is characterized by later onset and slowly progressive course.
P78363	Defects in ABCA4 may be a cause of age-related macular degeneration type 2 (ARMD2) [MIM:153800]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
P78363	Defects in ABCA4 are the cause of cone-rod dystrophy type 3 (CORD3) [MIM:604116]. CORDs are inherited retinal dystrophies belonging to the group of pigmentary retinopathies. CORDs are characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa.
P78363	Defects in ABCA4 are the cause of retinitis pigmentosa type 19 (RP19) [MIM:601718]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP19 is characterized by choroidal atrophy. Inheritance is autosomal recessive.
Q86UK0	Defects in ABCA12 are the cause of ichthyosis harlequin (HI) [MIM:242500]; also known as harlequin fetus. HI is a very severe skin disorder in which the neonate is born with a thick covering of armor-like scales. The skin dries out to form hard diamond-shaped plaques separated by fissures, resembling 'armor plating'. The normal facial features are severely affected, with distortion of the lips (eclabion), eyelids (ectropion), ears, and nostrils. Affected babies are often born prematurely and rarely survive the perinatal period.
Q86UK0	Defects in ABCA12 are the cause of ichthyosis lamellar type 2 (LI2) [MIM:601277]; also known as ichthyosis congenita IIB (ICR2B). LI is a non-bullous ichthyosis, a skin disorder characterized by abnormal cornification of the epidermis. It is one the most severe forms of ichthyoses apparent at birth and persisting throughout life. LI patients are born encased in a tight, shiny, translucent covering called collodion membrane. Over the first weeks of life, the collodion membrane is gradually replaced by generalized large, dark brown, plate-like scales with minimal to no erythroderma. Tautness of facial skin commonly results in ectropion, eclabium and scarring alopecia of the scalp. Common complications are severe heat intolerance and recurrent ear infections.
O75027	Defects in ABCB7 are the cause of X-linked sideroblastic anemia with ataxia (ASAT) [MIM:301310]. ASAT is a recessive disorder characterized by an infantile to early childhood onset of nonprogressive cerebellar ataxia and mild anemia with hypochromia and microcytosis.
O95342	Defects in ABCB11 are the cause of progressive familial intrahepatic cholestasis type 2 (PFIC2) [MIM:601847]. PFIC2 is an inherited liver disease of childhood which is characterized by cholestasis and normal serum gamma-glutamyltransferase activity. Defects in ABCB11 are also found in cases of chronic intrahepatic cholestasis without obvious familial history of chronic liver disease.
O95342	Defects in ABCB11 are the cause of benign recurrent intrahepatic cholestasis type 2 (BRIC2) [MIM:605479]. BRIC is characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration and patients are asymptomatic between episodes, both clinically and biochemically.
Q09428	Defects in ABCC8 are a cause of leucine-induced hypoglycemia (LIH) [MIM:240800]; also known as leucine-sensitive hypoglycemia of infancy. LIH is a rare cause of hypoglycemia and is described as a condition in which symptomatic hypoglycemia is provoked by high protein feedings. Hypoglycemia is also elicited by administration of oral or intravenous infusions of a single amino acid, leucine.
Q09428	Defects in ABCC8 are the cause of familial hyperinsulinemic hypoglycemia type 1 (HHF1) [MIM:256450]; also known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or congenital hyperinsulinism. HHF is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. It causes nesidioblastosis, a diffuse abnormality of the pancreas in which there is extensive, often disorganized formation of new islets. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.
Q09428	Defects in ABCC8 are a cause of permanent neonatal diabetes mellitus (PNDM) [MIM:606176]; also known as permanent diabetes mellitus of infancy (PDMI). PNDM is a rare form of diabetes characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.
Q09428	Defects in ABCC8 are the cause of transient neonatal diabetes mellitus type 2 (TNDM2) [MIM:610374]. Neonatal diabetes is a form of diabetes mellitus defined by the onset of mild-to- severe hyperglycemia within the first months of life. Transient neonatal diabetes remits early, with a possible relapse during adolescence.
O60706	Defects in ABCC9 are the cause of cardiomyopathy dilated type 1O (CMD1O) [MIM:608569]; also known as dilated cardiomyopathy with ventricular tachycardia. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
P33897	Defects in ABCD1 are the cause of adrenoleukodystrophy X- linked (X-ALD) [MIM:300100]. X-ALD is a peroxisomal metabolic disorder characterized by progressive multifocal demyelination of the central nervous system and by peripheral adrenal insufficiency (Addison disease). It results in mental deterioration, corticospinal tract dysfunction, and cortical blindness. Different clinical manifestations exist like: cerebral childhood ALD (CALD), adult cerebral ALD (ACALD), adrenomyeloneuropathy (AMN) and 'Addison disease only' (ADO) phenotype.
P33897	Microdeletions in ABCD1 are involved in the contiguous ABCD1/DXS1375E deletion syndrome (CADDS) [MIM:300475]. Patients manifest profound neonatal hypotonia, subsequent failure to thrive, and cholestatic liver disease.
Q9H222	Defects in ABCG5 are a cause of sitosterolemia [MIM:210250]; also known as phytosterolemia or shellfish sterolemia. It is a rare autosomal recessive disorder characterized by increased intestinal absorption of all sterols including cholesterol, plant and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Sitosterolemia patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease.
Q9H221	Genetic variations in ABCG8 can be associated with susceptibility to gallbladder disease type 4 (GBD4) [MIM:611465]. With an overall prevalence of 10-20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries.
Q9H221	Defects in ABCG8 are a cause of sitosterolemia [MIM:210250]; also known as phytosterolemia or shellfish sterolemia. It is a rare autosomal recessive disorder characterized by increased intestinal absorption of all sterols including cholesterol, plant and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Sitosterolemia patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease.
Q8WTS1	Defects in ABHD5 are the cause of Chanarin-Dorfman syndrome (CDS) [MIM:275630]; also called triglyceride storage disease with impaired long-chain fatty acid oxidation or neutral lipid storage disease with ichthyosis. CDS is an autosomal recessive inborn error of lipid metabolism with multisystemic accumulation of triglycerides although plasma concentrations are normal. Clinical characteristics are congenital generalized ichthyosis, vacuolated leukocytes, hepatomegaly, myopathy, cataracts, neurosensory hearing loss and developmental delay. The disorder presents at birth with generalized, fine, white scaling of the skin and a variable degree of erythema resembling non- bullous congenital ichthyosiform erythroderma.
Q5T2R7	A chromosomal aberration involving ABI1 is a cause of acute leukemias. Translocation t(10;11)(p11.2;q23) with MLL. ABI1 isoform 2 was found to be present in acute leukemia MLL-ABI1 fusion transcript.
P00519	A chromosomal aberration involving ABL1 is a cause of chronic myeloid leukemia (CML) [MIM:608232]. Translocation t(9;22)(q34;q11) with BCR. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
Q86WB2	Defects in ACACA are a cause of acetyl-CoA carboxylase 1 deficiency (ACACAD) [MIM:200350]; also known as ACAC deficiency or ACC deficiency. An inborn error of de novo fatty acid synthesis associated with severe brain damage, persistent myopathy and poor growth.
Q9UKU7	Defects in ACAD8 are the cause of isobutyryl-CoA dehydrogenase deficiency (IBDD) [MIM:611283]. The symptoms of IBDD generally appear until late in infancy or in childhood and can include poor feeding and growth (failure to thrive), a weakened and enlarged heart (dilated cardiomyopathy), seizures, and low numbers of red blood cells (anemia).
Q9H845	Defects in ACAD9 are a cause of acyl-CoA dehydrogenase family member type 9 deficiency (ACAD9 deficiency) [MIM:611126]. ACAD9 deficiency patients present with episodic liver dysfunction during otherwise mild illnesses or cardiomyopathy, along with chronic neurologic dysfunction.
P28330	Impaired ACADL activity results in non-ketotic hypoglycemia, hypotonia, muscle weakness and episodes of cardiorespiratory arrest associated with fasting [MIM:201460].
P11310	Defects in ACADM are the cause of medium-chain acyl-CoA dehydrogenase deficiency (MCAD deficiency) [MIM:201450]. It is an autosomal recessive disease which causes fasting hypoglycemia, hepatic dysfunction, and encephalopathy, often resulting in death in infancy. The disease frequency is one in 13000.
P16219	Defects in ACADS are the cause of short-chain acyl-CoA dehydrogenase deficiency (SCAD deficiency) [MIM:201470]. It is an autosomal recessive disorder resulting in acute acidosis and muscle weakness in infants, and a form of lipid-storage myopathy in adults.
P49748	Defects in ACADVL are the cause of very long chain acyl- CoA dehydrogenase deficiency (VLCAD deficiency) [MIM:201475]. VLCAD deficiency is an autosomal recessive disease which leads to impaired long-chain fatty acid beta-oxidation. It is clinically heterogeneous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting.
O00400	Defects in SLC33A1 are the cause of spastic paraplegia autosomal dominant type 42 (SPG42) [MIM:612539]. Spastic paraplegia is a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
P45954	Defects in ACADSB are the cause of short/branched-chain acyl-CoA dehydrogenase deficiency (SBCADD) [MIM:610006]; also known as 2-methylbutyryl-CoA dehydrogenase deficiency or 2- methylbutyryl glycinuria. SBCADD is an autosomal recessive disorder and consists of a defect in catabolism of L-isoleucine which is characterized by an increase of 2-methylbutyrylglycine and 2-methylbutyrylcarnitine in blood and urine. Affected individuals have seizures and psychomotor delay as the main clinical features.
Q5EE38	Defects in Acd are the cause of adrenocortical dysplasia (ACD). ACD is a spontaneous autosomal recessive mouse mutant resulting from spontaneous splicing mutation of acd. ACD mice are characterized by developmental defects in organs derived from the urogenital ridge, reduced survival, poor growth, skin hyperpigmentation and adrenal insufficiency. Forty percent of the mutants died within 24 hours. Analysis of E14.5 to E17.5 embryos revealed reduced formation of caudal structure as well as limb defects.
P12821	Genetic variations in ACE may be a cause of susceptibility to ischemic stroke [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
P12821	Defects in ACE are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).
P12821	Genetic variations in ACE could influence susceptibility to diabetic nephropathy [MIM:612624]; also called susceptibility to microvascular complications of diabetes type 3 (MVCD3) or susceptibility to diabetic end-stage renal disease (ESRD). Diabetic nephropathy is a kidney disease and resultant kidney function impairment due to the long standing effects of diabetes on the microvasculature (glomerulus) of the kidney. Features include increased urine protein and declining kidney function.
Q15822	Defects in CHRNA2 are the cause of nocturnal frontal lobe epilepsy type 4 (ENFL4) [MIM:610353]. ENFL4 is an autosomal dominant epilepsy characterized by nocturnal seizures associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking.
P32297	Genetic variations in CHRNA3 may be associated with susceptibility to lung cancer type 2 (LNCR2) [MIM:612052].
P32297	Genetic variations in CHRNA3 may be associated with susceptibility to peripheral arterial occlusive disease type 2 (PAOD2) [MIM:612052]. PAOD results from atherosclerosis of large and medium peripheral arteries, as well as the aorta. Many risk factors contribute to PAOD, including smoking, diabetes, hypertension, and hyperlipidemia. PAOD often coexists with coronary artery disease and cerebrovascular disease.
P43681	Defects in CHRNA4 are the cause of nocturnal frontal lobe epilepsy type 1 (ENFL1) [MIM:600513]; also symbolized ADNFLE. ENFL1 is an autosomal dominant epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements.
P30532	Genetic variations in CHRNA5 may be associated with susceptibility to lung cancer type 2 (LNCR2) [MIM:612052].
P02708	Defects in CHRNA1 are a cause of lethal type multiple pterygium syndrome [MIM:253290]. Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent.
P02708	The alpha subunit is the main focus for antibody binding in myasthenia gravis [MIM:254200]. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs.
P02708	Defects in CHRNA1 are a cause of congenital myasthenic syndrome slow-channel type (SCCMS) [MIM:601462]. SCCMS is the most common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. SCCMS is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes.
P02708	Defects in CHRNA1 are a cause of congenital myasthenic syndrome fast-channel type (FCCMS) [MIM:608930]. FCCMS is a congenital myasthenic syndrome characterized by kinetic abnormalities of the AChR. In most cases, FCCMS is due to mutations that decrease activity of the AChR by slowing the rate of opening of the receptor channel, speeding the rate of closure of the channel, or decreasing the number of openings of the channel during ACh occupancy. The result is failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
P17787	Defects in CHRNB2 are the cause of nocturnal frontal lobe epilepsy type 3 (ENFL3) [MIM:605375]. ENFL3 is an autosomal dominant epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements.
P11230	Defects in CHRNB1 are a cause of congenital myasthenic syndrome slow-channel type (SCCMS) [MIM:601462]. SCCMS is the most common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. SCCMS is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes.
P11230	Defects in CHRNB1 are a cause of congenital myasthenic syndrome with acetylcholine receptor deficiency (ACHRDCMS) [MIM:608931]. ACHRDCMS is a post-synaptic congenital myasthenic syndrome. Mutations underlying AChR deficiency cause a 'loss of function' and show recessive inheritance.
Q07001	Defects in CHRND are a cause of lethal type multiple pterygium syndrome [MIM:253290]. Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent.
Q07001	Defects in CHRND are a cause of congenital myasthenic syndrome slow-channel type (SCCMS) [MIM:601462]. SCCMS is the most common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. SCCMS is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes.
Q07001	Defects in CHRND are a cause of congenital myasthenic syndrome fast-channel type (FCCMS) [MIM:608930]. FCCMS is a congenital myasthenic syndrome characterized by kinetic abnormalities of the AChR. In most cases, FCCMS is due to mutations that decrease activity of the AChR by slowing the rate of opening of the receptor channel, speeding the rate of closure of the channel, or decreasing the number of openings of the channel during ACh occupancy. The result is failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
Q04844	The muscle AChR is the major target antigen in the autoimmune disease myasthenia gravis [MIM:254200]. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase- inhibiting drugs.
Q04844	Defects in CHRNE are a cause of congenital myasthenic syndrome slow-channel type (SCCMS) [MIM:601462]. SCCMS is the most common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. SCCMS is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes.
Q04844	Defects in CHRNE are a cause of congenital myasthenic syndrome fast-channel type (FCCMS) [MIM:608930]. FCCMS is a congenital myasthenic syndrome characterized by kinetic abnormalities of the AChR. In most cases, FCCMS is due to mutations that decrease activity of the AChR by slowing the rate of opening of the receptor channel, speeding the rate of closure of the channel, or decreasing the number of openings of the channel during ACh occupancy. The result is failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.
Q04844	Defects in CHRNE are a cause of congenital myasthenic syndrome with acetylcholine receptor deficiency (ACHRDCMS) [MIM:608931]. ACHRDCMS is a post-synaptic congenital myasthenic syndrome. Mutations underlying AChR deficiency cause a 'loss of function' and show recessive inheritance.
P07510	Defects in CHRNG are a cause of lethal type multiple pterygium syndrome [MIM:253290]. Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. Inheritance can be autosomal dominant, autosomal recessive, or X linked, but autosomal recessive inheritance appears to be most common. Clinical expression is very variable, and, in the severest form, lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia (e.g., chin to sternum, cervical, axillary, humero-ulnar, crural, popliteal, and ankles), and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies-in particular, cleft palate-are frequent.
P07510	Defects in CHRNG are a cause of Escobar syndrome [MIM:265000]; also known as Escobar variant of multiple pterygium syndrome or nonlethal type multiple pterygium syndrome. Escobar syndrome is a nonlethal form of arthrogryposis multiplex congenita. It is an autosomal recessive condition characterized by excessive webbing (pterygia), congenital contractures (arthrogryposis), and scoliosis. Variable other features include intrauterine death, congenital respiratory distress, short stature, faciocranial dysmorphism, ptosis, low-set ears, arachnodactyly and cryptorchism in males. Congenital contractures are common and may be caused by reduced fetal movements at sensitive times of development. Possible causes of decreased fetal mobility include space constraints such as oligohydramnion, drugs, metabolic conditions or neuromuscular disorders including myasthenia gravis.
P08172	Genetic variations in CHRM2 can influence susceptibility to major depressive disorder (MDD) [MIM:608516]. MDD is one of the most common psychiatric disorders. MDD is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning.
Q15067	Defects in ACOX1 are the cause of adrenoleukodystrophy pseudoneonatal (Pseudo-NALD) [MIM:264470]; also known as peroxisomal acyl-CoA oxidase deficiency. Pseudo-NALD is a peroxisomal single-enzyme disorder. Clinical features include mental retardation, leukodystrophy, seizures, mild hepatomegaly, hearing deficit. Pseudo-NALD is characterized by increased plasma levels of very-long chain fatty cids, due to decreased or absent peroxisome acyl-CoA oxidase activity. Peroxisomes are intact and functioning.
O60488	Defects in ACSL4 are the cause of mental retardation X- linked type 63 (MRX63) [MIM:300387]. Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non- syndromic mental retardation patients do not manifest other clinical signs.
O60488	Defects in ACSL4 may be a cause of AMME complex [MIM:300194]; also known as Alport syndrome with mental retardation, midface hypoplasia and elliptocytosis. The AMME complex is a contiguous gene deletion syndrome.
Q9UKU0	A chromosomal aberration involving ACSL6 may be a cause of myelodysplastic syndrome with basophilia. Translocation t(5;12)(q31;p13) with ETV6.
Q9UKU0	A chromosomal aberration involving ACSL6 may be a cause of acute myelogenous leukemia with eosinophilia. Translocation t(5;12)(q31;p13) with ETV6.
Q9UKU0	A chromosomal aberration involving ACSL6 may be a cause of acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ETV6.
P62736	Defects in ACTA2 are the cause of aortic aneurysm familial thoracic type 6 (AAT6) [MIM:611788]. AATs are characterized by permanent dilation of the thoracic aorta usually due to degenerative changes in the aortic wall. They are primarily associated with a characteristic histologic appearance known as 'medial necrosis' or 'Erdheim cystic medial necrosis' in which there is degeneration and fragmentation of elastic fibers, loss of smooth muscle cells, and an accumulation of basophilic ground substance.
Q96HG5	Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:607371]. DYTJ is a form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTJ patients manifest progressive, generalized, dopa- unresponsive dystonia, developmental malformations and sensory hearing loss.
P68032	Defects in ACTC1 are the cause of cardiomyopathy dilated type 1R (CMD1R) [MIM:102540]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
P68032	Defects in ACTC1 are the cause of cardiomyopathy familial hypertrophic type 11 (CMH11) [MIM:612098]. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
P68032	Defects in ACTC1 are the cause of atrial septal defect type 5 (ASD5) [MIM:612794]. A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria.
P63261	Defects in ACTG1 are the cause of non-syndromic sensorineural deafness autosomal dominant type 20 (DFNA20) [MIM:604717]; also called autosomal dominant deafness type 26 (DFNA26). DFNA20 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Q01718	Defects in MC2R are the cause of glucocorticoid deficiency type 1 (GCCD1) [MIM:202200]; also known as familial glucocorticoid deficiency type 1 (FGD1). GCCD1 is an autosomal recessive disorder due to congenital insensitivity or resistance to adrenocorticotropin (ACTH). It is characterized by progressive primary adrenal insufficiency, without mineralocorticoid deficiency.
P35609	Defects in ACTN2 are the cause of cardiomyopathy dilated type 1AA (CMD1AA) [MIM:612158]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
O43707	Defects in ACTN4 are the cause of focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278]. FSGS1 is a common renal lesion characterized by increased urinary protein excretion (proteinuria) and decreasing kidney function (nephrotic syndrome). Renal insufficiency often progresses to end-stage renal disease (ESRD) (also known as end-stage renal failure), a highly morbid state requiring either dialysis therapy or kidney transplantation. FSGS1 is defined by the presence of segmental sclerosis in glomeruli, and is seen in all ethnic groups, although it is particularly common in individuals of African descent. FSGS1 occurs as an isolated primary condition or secondary to disorders as HIV infection, obesity, hypertension and diabetes. FSGS1 may also be inherited as a Mendelian trait.
P68133	Defects in ACTA1 are the cause of nemaline myopathy type 3 (NEM3) [MIM:161800]. A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-or rod-like structures in muscle fibers on histologic examination.
P68133	Defects in ACTA1 are a cause of congenital myopathy with excess of thin myofilaments (CM) [MIM:102610].
P68133	Defects in ACTA1 are a cause of congenital myopathy with fiber-type disproportion (CFTD) [MIM:255310]; also known as congenital fiber-type disproportion myopathy (CFTDM). CFTD is a genetically heterogeneous disorder in which there is relative hypotrophy of type 1 muscle fibers compared to type 2 fibers on skeletal muscle biopsy. However, these findings are not specific and can be found in many different myopathic and neuropathic conditions.
P37023	Defects in ACVRL1 are the cause of hereditary hemorrhagic telangiectasia type 2 (HHT2) [MIM:600376]; also known as Osler- Rendu-Weber syndrome 2 (ORW2). HHT2 is an autosomal dominant multisystemic vascular dysplasia, characterized by recurrent epistaxis, muco-cutaneous telangiectases, gastro-intestinal hemorrhage, and pulmonary, cerebral and hepatic arteriovenous malformations; all secondary manifestations of the underlying vascular dysplasia.
Q04771	Defects in ACVR1 are a cause of fibrodysplasia ossificans progressiva (FOP) [MIM:135100]. FOP is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. Heterotopic ossification in FOP begins in childhood and can be induced by trauma or may occur without warning. Bone formation is episodic and progressive, leading to extra-articular ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible.
Q03154	Defects in ACY1 are the cause of aminoacylase-1 deficiency (ACY1D) [MIM:609924]. ACY1D results in a metabolic disorder manifesting with encephalopathy, unspecific psychomotor delay, psychomotor delay with atrophy of the vermis and syringomyelia, marked muscular hypotonia or normal clinical features. Epileptic seizures are a frequent feature. All affected individuals exhibit markedly increased urinary excretion of several N-acetylated amino acids.
P45381	Defects in ASPA are the cause of Canavan disease (CAND) [MIM:271900]; also known as spongy degeneration of the brain. CAND is a rare neurodegenerative condition of infancy or childhood characterized by white matter vacuolization and demeylination that gives rise to a spongy appearance. The clinical features are onset in early infancy, atonia of neck muscles, hypotonia, hyperextension of legs and flexion of arms, blindness, severe mental defect, megalocephaly, and death by 18 months on the average.
Q9BZ11	Genetic variations in ADAM33 are associated with susceptibility to asthma (ASTHMA) [MIM:600807]. The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with weezing due to spasmodic contraction of the bronchi.
Q13443	Defects in ADAM9 are the cause of cone-rod dystrophy type 9 (CORD9) [MIM:612775]. An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa.
O00116	Defects in AGPS are the cause of rhizomelic chondrodysplasia punctata type 3 (RCDP3) [MIM:600121]. RCDP3 is characterized by rhizomelic shortening of femur and humerus, vertebral disorders, cataract, cutaneous lesions and severe mental retardation.
P00813	Defects in ADA are the cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell- negative/NK-cell-negative due to adenosine deaminase deficiency (ADASCID) [MIM:102700]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development. ADA-SCID is an autosomal recessive form accounting for about 50% of non-X-linked SCIDs. ADA deficiency has been diagnosed in chronically ill teenagers and adults (late or adult onset). Population and newborn screening programs have also identified several healthy individuals with normal immunity who have partial ADA deficiency.
Q8NI60	Defects in CABC1 are a cause of coenzyme Q10 deficiency [MIM:607426]; also known as primary CoQ10 deficiency. Coenzyme Q10 deficiency patients present a progressive neurological disorder with cerebellar atrophy, developmental delay, and hyperlactatemia.
Q8NI60	Defects in CABC1 are the cause of spinocerebellar ataxia autosomal recessive type 9 (SCAR9) [MIM:612016]; also known as autosomal recessive cerebellar ataxia type 2 (ARCA2). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR9 is an autosomal recessive form characterized by gait ataxia and cerebellar atrophy with slow progression and few associated features. Patients can manifest brisk tendon reflexes and Hoffmann sign, mild psychomotor retardation, mild axonal degeneration of the sural nerve, exercise intolerance and elevated serum lactate.
Q96PN6	Genetic variations in ADCY10 are associated with absorptive hypercalciuria type 2 (HCA2) [MIM:143870]. Absorptive hypercalciuria (AH) is a common cause of calcium oxalate nephrolithiasis. Clinically, AH is characterized by intestinal hyperabsorption of calcium in the presence of normal serum calcium and immunoreactive PTH (iPTH). It is often accompanied by low bone mineral density (BMD), particularly of the lumbar spine. About 50% of patients with AH present with a family history of calcium oxalate nephrolithiasis and hypercalciuria.
Q15848	Defects in ADIPOQ are the cause of adiponectin deficiency (ADPND) [MIM:612556]. ADPND results in very low concentrations of plasma adiponectin.
Q15848	Genetic variations in ADIPOQ are associated with non- insulin-dependent diabetes mellitus (NIDDM) [MIM:125853]; also known as diabetes mellitus type 2. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance.
P12235	Defects in SLC25A4 are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 2 (PEOA2) [MIM:609283]. Progressive external ophthalmoplegia is characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged- red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.
P55197	A chromosomal aberration involving MLLT10 is associated with acute leukemias. Translocation t(10;11)(p12;q23) with MLL/HRX. The result is a rogue activator protein.
P55197	A chromosomal aberration involving MLLT10 is associated with diffuse histiocytic lymphomas. Translocation t(10;11)(p13;q14) with PICALM.
P55198	A chromosomal aberration involving MLLT6 is associated with acute leukemias. Translocation t(11;17)(q23;q21) with MLL/HRX. The result is a rogue activator protein.
Q13015	A chromosomal aberration involving MLLT11 is found in acute leukemias. Translocation t(1;11)(q21;q23) with MLL.
P42568	A chromosomal aberration involving MLLT3 is associated with acute leukemias. Translocation t(9;11)(p22;q23) with MLL/HRX. The result is a rogue activator protein.
P55196	A chromosomal aberration involving MLLT4 is associated with acute leukemias. Translocation t(6;11)(q27;q23) with MLL/HRX. The result is a rogue activator protein.
P51825	A chromosomal aberration involving AFF1 is associated with acute leukemias. Translocation t(4;11)(q21;q23) with MLL/HRX. The result is a rogue activator protein.
Q13521	Defects in AFF2 are the cause of FRAXE [MIM:309548]. FRAXE is an X-linked form of mental retardation. Loss of FMR2 expression is correlated with FRAXE CCG(N) expansion. Normal individuals have 6-35 copies of the repeat, whereas cytogenetically positive, developmentally delayed males have more than 200 copies and show methylation of the associated CPG island.
Q9UHB7	A chromosomal aberration involving AFF4 is found in acute lymphoblastic leukemia (ALL). Insertion ins(5;11)(q31;q13q23) that forms a MLL-AFF4 fusion protein.
P06280	Defects in GLA are the cause of Fabry disease (FD) [MIM:301500]. FD is a rare X-linked sphingolipidosis disease where glycolipid accumulates in many tissues. The disease consists of an inborn error of glycosphingolipid catabolism. FD patients show systemic accumulation of globotriaoslyceramide (Gb3) and related glycosphingolipids in the plasma and cellular lysosomes throughout the body. Clinical recognition in males results from characteristic skin lesions (angiokeratomas) over the lower trunk. Patients may show ocular deposits, febrile episodes, and burning pain in the extremities. Death results from renal failure, cardiac or cerebral complications of hypertension or other vascular disease. Heterozygous females may exhibit the disorder in an attenuated form, they are more likely to show corneal opacities.
Q8N302	Defects in AGGF1 are a cause of Klippel-Trenaunay syndrome (KTS) [MIM:149000]. KTS is a congenital disease characterized by malformations of capillary (98% of KTS patients), venous (72%) and lymphatic (11%) vessels, and bony and soft tissue hypertrophy that leads to large cutaneous hemangiomata with hypertrophy of the related bones and soft tissues.
O00253	Defects in AGRP may be a cause of autosomal dominant obesity [MIM:601665].
P30556	Defects in AGTR1 are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).
Q8N157	Defects in AHI1 are the cause of Joubert syndrome type 3 (JBTS3) [MIM:608629]. JBTS is an autosomal recessive disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. JBTS3 shows minimal extra central nervous system involvement and appears not to be associated with renal dysfunction.
Q9GZX7	Defects in AICDA are the cause of autosomal recessive hyper-IgM immunodeficiency syndrome type 2 (HIGM2) [MIM:605258]. HIGM2 is characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE, resulting in a profound susceptibility to bacterial infections. HIGM2 causes the absence of Ig class switch recombination (CSR), the lack of Ig somatic hypermutations, and lymph node hyperplasia caused by the presence of giant germinal centers.
Q9NZN9	Defects in AIPL1 are the cause of Leber congenital amaurosis type 4 (LCA4) [MIM:604393]. LCA designates a clinically and genetically heterogeneous group of childhood retinal degenerations, generally inherited in an autosomal recessive manner. Affected infants have little or no retinal photoreceptor function as tested by electroretinography. LCA represents the most common genetic cause of congenital visual impairment in infants and children.
O00170	Defects in AIP are a cause of pituitary adenoma predisposition (PAP) [MIM:102200]. Pituitary adenomas include somatotropinoma and prolactinoma.
O00170	Defects in AIP are a cause of familial isolated pituitary adenoma (FIPA) [MIM:102200].
O00170	Defects in AIP are a cause of growth hormone-secreting pituitary adenoma [MIM:102200]; also known as familial isolated somatotropinomas (FIS) or isolated familial somatotropinoma (IFS) or familial somatotrophinoma or acromegaly due to pituitary adenoma.
O00170	Defects in AIP are a cause of ACTH-secreting pituitary adenoma (ASPA) [MIM:219090]; also known as pituitary Cushing disease. A pituary adenoma resulting in excessive production of adrenocorticotropic hormone. This leads to hypersecretion of cortisol by the adrenal glands and ACTH-dependent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and trunkal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.
O00170	Defects in AIP are a cause of prolactin-secreting pituitary adenoma [MIM:600634]; also known as prolactinoma. Prolactin-secreting pituitary adenoma is the most common type of hormonally active pituitary adenoma.
O43918	Defects in AIRE are a cause of autoimmune poly- endocrinopathy candidiasis ectodermal dystrophy (APECED) [MIM:240300]; also known as autoimmune polyglandular syndrome type I (APS-1). APECED is an autosomal recessive disease characterized by: (1) autoimmune polyendocrinopathies: hypoparathyroidism, adrenocortical failure, IDDM, gonadal failure, hypothyroidism, pernicious anemia, and hepatitis; (2) chronic mucocutaneous candidiasis; (3) ectodermal dystrophies: vitiligo, alopecia, keratopathy, dystrophy of dental enamel, nails and tympanic membranes. In addition, a high proportion of patients develop squamous cell carcinoma of the oral mucosa. The disease is reported worldwide but is exceptionally prevalent among the Finnish population (incidence 1:25000) and the Iranian jews (incidence 1:9000).
O43918	Most of the mutations alter the nucleus-cytoplasm distribution of AIRE and disturb its association with nuclear dots and cytoplasmic filaments. Most of the mutations also decrease transactivation of the protein. The HSR domain is responsible for the homomultimerization activity of AIRE. All the missense mutations of the HSR and the SAND domains decrease this activity, but those in other domains do not. The AIRE protein is present in soluble high-molecular-weight complexes. Mutations in the HSR domain and deletion of PHD zinc fingers disturb the formation of these complexes.
P51857	Defects in AKR1D1 are the cause of congenital bile acid synthesis defect type 2 (CBAS2) [MIM:235555]; also known as cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency. Patients with this liver disease show absence or low levels of chenodeoxycholic acid and cholic acid in plasma and urine.
Q9UQH3	Defects in AKAP9 are the cause of long QT syndrome type 11 (LQT11) [MIM:611820]. Long QT syndromes are heart disorders characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to excercise or emotional stress. They can present with a sentinel event of sudden cardiac death in infancy.
P31749	Defects in AKT1 are associated with breast cancer (BC) [MIM:114480]. BC is an extremely common malignancy, affecting one in eight women during their lifetime.
P31749	Defects in AKT1 are associated with colorectal cancer (CRC) [MIM:114500].
P31749	Defects in AKT1 are associated with susceptibility to ovarian cancer [MIM:604370]; also called susceptibility to familial breast-ovarian cancer type 1 (BROVCA1).
Q64362	Defects in Aktip are a cause of embryonic death in homozygous animals. Death occurs at about 10 days of development. Symptoms include loss of left-right asymmetry, malformation of the developing brain and of the spinal cord, syndactyly and polydactyly. Heterozygous animals are characterized by polydactyly and thymic hyperplasia.
P51648	Defects in ALDH3A2 are the cause of Sjoegren-Larsson syndrome (SLS) [MIM:270200]. SLS is an autosomal recessive neurocutaneous disorder characterized by a combination of severe mental retardation, spastic di- or tetraplegia and congenital ichthyosis (increased keratinization). Ichthyosis is usually evident at birth, neurologic symptoms appear in the first or second year of life. Most patients have an IQ of less than 60. Additional clinical features include glistening white spots on the retina, seizures, short stature and speech defects.
P30038	Defects in ALDH4A1 are the cause of hyperprolinemia type 2 (HP2) [MIM:239510]. HP2 is characterized by the accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. The disorder may be causally related to neurologic manifestations, including seizures and mental retardation.
P20292	Genetic variations in ALOX5AP may be a cause of susceptibility to ischemic stroke [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
P20292	Haplotypes HapA and HapB are associated with susceptibility to myocardial infarction [MIM:608557].
P49419	Defects in ALDH7A1 are the cause of pyridoxine-dependent epilepsy (PDE) [MIM:266100]. PDE is characterized by a combination of various seizure types. It usually occurs in the first hours of life and is unresponsive to standard anticonvulsants, responding only to immediate administration of pyridoxine hydrochloride.
Q9P157	Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:103600]. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.
P04075	Defects in ALDOA are the cause of glycogen storage disease type 12 (GSD12) [MIM:611881]; also known as red cell aldolase deficiency. A metabolic disorder associated with increased hepatic glycogen and hemolytic anemia. It may lead to myopathy with exercise intolerance and rhabdomyolysis.
P05062	Defects in ALDOB are the cause of hereditary fructose intolerance (HFI) [MIM:229600]. HFI is an autosomal recessive disease that results in an inability to metabolize fructose and related sugars. Complete exclusion of fructose results in dramatic recovery; however, if not treated properly, HFI subjects suffer episodes of hypoglycemia, general ill condition, and risk of death the remainder of life.
P84996	Defects in GNAS are the cause of GNAS hyperfunction [MIM:139320]. This condition is characterized by increased trauma- related bleeding tendency, prolonged bleeding time, brachydactyly and mental retardation. Both the XLas isoforms and the ALEX protein are mutated which strongly reduces the interaction between them and this may allow unimpeded activation of the XLas isoforms.
P84996	Defects in GNAS are a cause of ACTH-independent macronodular adrenal hyperplasia (AIMAH) [MIM:219080]; also known as adrenal Cushing syndrome due to AIMAH. A rare adrenal defect characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and trunkal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.
P84996	Genetic variations in GNAS are the cause of pseudohypoparathyroidism type 1B (PHP1B) [MIM:603233]. PHP1B is characterized by parathyroid hormone (PTH)-resistant hypocalcemia and hyperphosphatemia. Patients affected with PHP1B have normal activity of the product of GNAS, lack developmental defects characteristic of AHO, and typically show no other endocrine abnormalities besides resistance to PTH. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed.
P84996	Defects in GNAS may be a cause of colorectal cancer (CRC) [MIM:114500].
Q9BV10	Defects in ALG12 are the cause of congenital disorder of glycosylation type 1G (CDG1G) [MIM:607143]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q9BT22	Defects in ALG1 are the cause of congenital disorder of glycosylation type 1K (CDG1K) [MIM:608540]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q9H553	Defects in ALG2 are the cause of congenital disorder of glycosylation type 1I (CDG1I) [MIM:607906]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q92685	Defects in ALG3 are the cause of congenital disorder of glycosylation type 1D (CDG1D) [MIM:601110]; also known as carbohydrate-deficient glycoprotein syndrome type IV (CDGS4). CDGs are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. They are characterized by under-glycosylated serum glycoproteins.
Q9Y672	Defects in ALG6 are the cause of congenital disorder of glycosylation type 1C (CDG1C) [MIM:603147]; also known as carbohydrate-deficient glycoprotein syndrome type V. CDGs are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. They are characterized by under-glycosylated serum glycoproteins. CDG1C patients have muscular hypotonia, show a delayed statomotor development and are mentally retarded. CDG1C is biochemically characterized by an accumulation of dolichyl pyrophosphate-linked Man(9)GlcNAc(2) in the endoplasmic reticulum.
Q9BVK2	Defects in ALG8 are the cause of congenital disorder of glycosylation type 1H (CDG1H) [MIM:608104]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q9H6U8	A chromosomal aberration involving ALG9 is found in a family with bipolar affective disorder. Translocation t(9;11)(p24;q23).
Q9H6U8	Defects in ALG9 are the cause of congenital disorder of glycosylation type 1L (CDG1L) [MIM:608776]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q9UM73	A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas.
Q9UM73	A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A.
Q9UM73	A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17.
Q8TCU4	Defects in ALMS1 are the cause of Alstrom syndrome (ALMS) [MIM:203800]. Alstrom syndrome is a rare autosomal recessive disorder characterized by progressive cone-rod retinal dystrophy, neurosensory hearing loss, early childhood obesity and type 2 diabetes mellitus. Dilated cardiomyopathy, acanthosis nigricans, male hypogonadism, hypothyroidism, developmental delay and hepatic dysfunction can also be associated with the syndrome.
Q9HCF4	A chromosomal aberration involving ALO17 is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALK.
Q96Q42	Defects in ALS2 are the cause of amyotrophic lateral sclerosis type 2 (ALS2) [MIM:205100]. ALS2 is a familial form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper and lower motor neurons and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of cases leading to familial forms.
Q96Q42	Defects in ALS2 are the cause of juvenile primary lateral sclerosis (JPLS) [MIM:606353]. JPLS is a neurodegenerative disorder which is closely related to but clinically distinct from amyotrophic lateral sclerosis. It is a progressive paralytic disorder which results from dysfunction of the upper motor neurons of the motor cortex while the lower neurons are unaffected.
Q96Q42	Defects in ALS2 are the cause of infantile-onset ascending spastic paralysis (IAHSP) [MIM:607225]. IAHSP is characterized by progressive spasticity and weakness of limbs.
Q9H161	Defects in ALX4 are the cause of parietal foramina 2 (PFM2) [MIM:609597]; also known as foramina parietalia permagna (FPP). PFM2 is an autosomal dominant disease characterized by oval defects of the parietal bones caused by deficient ossification around the parietal notch, which is normally obliterated during the fifth fetal month. PFM2 is also a clinical feature of Potocki- Shaffer syndrome.
Q9H161	Involved in Potocki-Shaffer syndrome (PSS) [MIM:601224]. PSS is a contiguous gene syndrome caused by deletion of the 11p11.2 region.
O35137	Defects in Alx4 are the cause of Strong luxoid (lst) phenotype. At heterozygosity lst is characterized by preaxial abnormalities of the hindfeet and, very rarely, of the forefeet. Homozygotes show preaxial polydactyly of all four limbs, reductions and duplications of the radius, absence of the tibia, craniofacial defects, reduction of the pubis, and dorsal alopecia.
Q9UHK6	Defects in AMACR are the cause of alpha-methylacyl-CoA racemase deficiency (AMACRD) [MIM:604489]. AMACRD results in elevated plasma concentrations of pristanic acid C27-bile-acid intermediates. It can be associated with polyneuropathy, retinitis pigmentosa, epilepsy.
Q9UHK6	Defects in AMACR are the cause of congenital bile acid synthesis defect type 4 (CBAS4) [MIM:214950]; also known as cholestasis, intrahepatic, with defective conversion of trihydroxycoprostanic acid to cholic acid or trihydroxycoprostanic acid in bile. Clinical features include neonatal jaundice, intrahepatic cholestasis, bile duct deficiency and absence of cholic acid from bile.
Q99217	Defects in AMELX are the cause of amelogenesis imperfecta hypoplastic type 1 (AIH1) [MIM:301200]. AIH1 is a X-linked defect of dental enamel formation. Teeth have only a thin layer of enamel with normal hardness. The thinness of the enamel makes the teeth appear small.
Q9Y4X0	Defects in AMMECR1 may be a cause of AMME complex [MIM:300194]; also known as Alport syndrome with mental retardation, midface hypoplasia and elliptocytosis. The AMME complex is a contiguous gene deletion syndrome.
Q16671	Defects in AMHR2 are the cause of persistent Muellerian duct syndrome type 2 (PMDS2) [MIM:261550]. PMDS2 is a form of male pseudohermaphroditism characterized by a failure of Muellerian duct regression in otherwise normal males.
Q6UKI2	Defects in AMN could be a cause of a canine form of megaloblastic anemia 1 (MGA1).
Q9BXJ7	Defects in AMN are a cause of recessive hereditary megaloblastic anemia 1 (MGA1) [MIM:261100]; also known as MGA1 Norwegian type or Imerslund-Grasbeck syndrome (I-GS). MGA1 is due to selective malabsorption of vitamin B12. Defects in vitamin B12 absorption lead to impaired function of thymidine synthase. As a consequence DNA synthesis is interrupted. Rapidly dividing cells involved in erythropoiesis are particularly affected.
P23109	Defects in AMPD1 are the cause of adenosine monophosphate deaminase deficiency muscle type (AMPDDM) [MIM:102770]. AMPDDM is a metabolic disorder resulting in exercise-related myopathy. It is characterized by exercise-induced muscle aches, cramps, and early fatigue.
Q01432	Defects in AMPD3 are the cause of adenosine monophosphate deaminase deficiency erythrocyte type (AMPDDE) [MIM:102772]. AMPDDE is a metabolic disorder due to lack of activity of the erythrocyte isoform of AMP deaminase. It is a clinically asymptomatic condition characterized by a 50% increase in steady- state levels of ATP in affected cells. Individuals with complete deficiency of erythrocyte AMP deaminase are healthy and have no hematologic disorders.
P30533	In complex with the alpha-2-MR or gp330, it may have some role in the pathogenesis of membrane glomerular nephritis.
P54802	Defects in NAGLU are the cause of mucopolysaccharidosis type 3B (MPS3B) [MIM:252920]; also known as Sanfilippo syndrome B. MPS3B is a form of mucopolysaccharidosis type 3, an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate. MPS3 is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life.
P10275	Defects in AR are the cause of androgen insensitivity syndrome (AIS) [MIM:300068]; previously known as testicular feminization syndrome (TFM). AIS is an X-linked recessive form of pseudohermaphroditism due end-organ resistance to androgen. Affected males have female external genitalia, female breast development, blind vagina, absent uterus and female adnexa, and abdominal or inguinal testes, despite a normal 46,XY karyotype.
P10275	Defects in AR are the cause of spinal and bulbar muscular atrophy X-linked type 1 (SMAX1) [MIM:313200]; also known as Kennedy disease. SMAX1 is an X-linked recessive form of spinal muscular atrophy. Spinal muscular atrophy refers to a group of neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. SMAX1 occurs only in men. Age at onset is usually in the third to fifth decade of life, but earlier involvement has been reported. It is characterized by slowly progressive limb and bulbar muscle weakness with fasciculations, muscle atrophy, and gynecomastia. The disorder is clinically similar to classic forms of autosomal spinal muscular atrophy. SMAX1 is caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
P10275	Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor.
P10275	Defects in AR are the cause of androgen insensitivity syndrome partial (PAIS) [MIM:312300]; also known as Reifenstein syndrome. PAIS is characterized by hypospadias, hypogonadism, gynecomastia, genital ambiguity, normal XY karyotype, and a pedigree pattern consistent with X-linked recessive inheritance. Some patients present azoospermia or severe oligospermia without other clinical manifestations.
P15207	Defects in Ar are a cause of androgen insensitivity. Rats with this syndrome are called testicular feminized (TFM).
P01160	Defects in NPPA are the cause of atrial fibrillation familial type 6 (ATFB6) [MIM:612201]. Atrial fibrillation is a common disorder of cardiac rhythm that is hereditary in a small subgroup of patients. It is characterized by disorganized atrial electrical activity, progressive deterioration of atrial electromechanical function and ineffective pumping of blood into the ventricles. It can be associated with palpitations, syncope, thromboembolic stroke, and congestive heart failure.
P03950	Defects in ANG are the cause of susceptibility to amyotrophic lateral sclerosis type 9 (ALS9) [MIM:611895]. ALS is a degenerative disorder of motor neurons in the cortex, brain stem and spinal cord. ALS is characterized by muscular weakness and atrophy.
Q9Z1P8	Elevated levels of expression in models of obesity and diabetes.
P01019	Defects in AGT are associated with susceptibility to essential hypertension [MIM:145500]. Hypertension also occurs in 5-7% of all pregnancies where it is a leading cause of maternal, fetal and neonatal morbidity and mortality. Among pregnancy- induced hypertension cases, severe pre-eclampsia [MIM:189800] is characterized by the development of hypertension and proteinuria after the 20th week of pregnancy and is the most distinctive, life-threatening form.
P01019	Defects in AGT are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype).
P16157	Defects in ANK1 are a cause of spherocytosis type 1 (SPH1) [MIM:182900]; also called hereditary spherocytosis type 1 (HS1). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Inheritance can be autosomal dominant or recessive.
Q01484	Defects in ANK2 are the cause of long QT syndrome type 4 (LQT4) [MIM:600919]; also known as sick sinus syndrome with bradycardia. Long QT syndromes are heart disorders characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress. LQT4 displays many atypical features compared to classical long QT syndromes, including pronounced sinus bradycardia, polyphasic T waves and atrial fibrillation. Cardiac repolarization defects may be not as severe as in classical LQT syndromes and prolonged QT interval on EKG is not a consistent feature.
Q9HCJ1	Defects in ANKH are the cause of chondrocalcinosis 2 (CCAL2) [MIM:118600]. Chondrocalcinosis is a common cause of joint pain and arthritis caused by calcium deposition in articular cartilage and the presence of calcium hypophosphate crystals in synovial fluid, cartilage and periarticular soft tissue. CCAL2 inheritance is autosomal dominant.
Q9HCJ1	Defects in ANKH are the cause of craniometaphyseal dysplasia Jackson type (CMDJ) [MIM:123000]. CMDJ is a rare autosomal dominant skeletal disorder characterized by abnormal bone formation and mineralization in membranous as well as endochondral bones. Progressive thickening of the bones can cause narrowing of cranial foramina and can lead to severe visual and neurological impairment, such as facial palsy and deafness.
Q9JHZ2	Defects in Ankh are the cause of a generalized, progressive form of arthritis. In ank mice hydroxyapatite crystals develop in articular surfaces and synovial fluid leading to joint space narrowing, cartilage erosion, and formation of bony outgrowths or osteophytes that cause fusion and joint immobility and destruction.
Q15327	Defects in ANKRD1 may be a cause of total anomalous pulmonary venous return (TAPVR) [MIM:106700]. TAPVR is a rare congenital heart disease (CHD) in which the pulmonary veins fail to connect to the left atrium during cardiac development, draining instead into either the right atrium or one of its venous tributaries. This disease accounts for 1.5% of all CHDs and has a prevalence of approximately 1 out of 15'000 live births.
P0C0T2	Defects in Anks6 are the cause of polycystic kidney disease (cy). Heterozygous cy rats are characterized by progressive formation and enlargement of cysts in kidneys.
Q75V66	Defects in ANO5 are the cause of gnathodiaphyseal dysplasia (GDD) [MIM:166260]; also known as osteogenesis imperfecta with unusual skeletal lesions or gnathodiaphyseal sclerosis. GDD is a rare skeletal syndrome characterized by bone fragility, sclerosis of tubular bones, and cemento-osseous lesions of the jawbone. Patients experience frequent bone fractures caused by trivial accidents in childhood; however the fractures heal normally without bone deformity. The jaw lesions replace the tooth-bearing segments of the maxilla and mandible with fibrous connective tissues, including various amounts of cementum-like calcified mass, sometimes causing facial deformities. Patients also have a propensity for jaw infection and often suffer from purulent osteomyelitis-like symptoms, such as swelling of and pus discharge from the gums, mobility of the teeth, insufficient healing after tooth extraction and exposure of the lesions into the oral cavity.
P20594	Defects in NPR2 are the cause of acromesomelic dysplasia Maroteaux type (AMDM) [MIM:602875]. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs, and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMDM is an autosomal recessive form characterized by axial skeletal involvement with wedging of vertebral bodies. In AMDM all skeletal elements are present but show abnormal rates of linear growth.
P70180	Defects in Npr3 are the cause of a number of skeletal- overgrowth phenotypes, Longjohn (Lgj), Longjohn-2J (Lgj-2J) and Strigosus (Stri). These are all recessive conditions characterized by an elongated body, thoracic kyphosis, arachnodactyly, and sacral and/or tail kinks, but no significant changes in craniofacial structures.
Q9UC78	Defects in SERPINC1 are the cause of antithrombin-III deficiency (AT3D) [MIM:107300]. AT3D is an important risk factor for hereditary thrombophilia, a hemostatic disorder characterized by a tendency to recurrent thrombosis. AT3D is classified into 4 types. Type I: characterized by a 50% decrease in antigenic and functional levels. Type II: has defects affecting the thrombin- binding domain. Type III: alteration of the heparin-binding domain. Plasma AT-III antigen levels are normal in type II and III. Type IV: consists of miscellaneous group of unclassifiable mutations.
P58335	Defects in ANTXR2 are the cause of infantile systemic hyalinosis (ISH) [MIM:236490]. This autosomal recessive syndrome is similar to JHF, but has an earlier onset and a more severe course. Symptoms appear at birth or within the first months of life, with painful, swollen joint contractures, osteopenia, osteoporosis and livid red hyperpigmentation over bony prominences. Patients develop multiple subcutaneous skin tumors and gingival hypertrophy. Hyaline deposits in multiple organs, recurrent infections and intractable diarrhea often lead to death within the first 2 years of life. Surviving children may suffer from severely reduced mobility due to joint contractures.
P58335	Defects in ANTXR2 are the cause of juvenile hyaline fibromatosis (JHF) [MIM:228600]. JHF is an autosomal recessive syndrome that is similar to ISH but takes a milder course. It is characterized by hyaline deposition in the dermis, multiple subcutaneous skin tumors and gingival hypertrophy, followed by progressive joint contractions, osteopenia and osteoporosis that may lead to a severe limitation of mobility.
P21397	Defects in MAOA are the cause of Brunner syndrome (BRUNS) [MIM:300615]. Brunner syndrome is a form of X-linked non- dysmorphic mild mental retardation. Male patients are affected by a syndrome of borderline mental retardation and exhibit abnormal behavior, including disturbed regulation of impulsive aggression. Obligate female carriers have normal intelligence and behavior.
P56377	Defects in AP1S2 are the cause of mental retardation X- linked type 59 (MRX59) [MIM:300630]. It is characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. In contrast to syndromic or specific X-linked mental retardation which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation. MRX59 consists of a mild-to-profound mental retardation. Other features includes hypotonia early in life and delay in walking.
P05549	Defects in TFAP2A are the cause of branchiooculofacial syndrome (BOFS) [MIM:113620]; also known as branchial clefts with characteristic facies, growth retardation, imperforate nasolacrimal duct, and premature aging or lip pseudocleft- hemangiomatous branchial cyst syndrome. BOFS is a rare autosomal dominant cleft palate craniofacial disorder with variable expressivity. The major features include cutaneous anomalies, ocular anomalies, characteristic facial appearance (malformed pinnae, oral clefts), and, less commonly, renal and ectodermal (dental and hair) anomalies.
Q92481	Defects in TFAP2B are the cause of Char syndrome (CHAR) [MIM:169100]. CHAR is an autosomal dominant disorder characterized by patent ductus arteriosus (PDA), facial dysmorphism and hand anomalies.
O00203	Defects in AP3B1 are the cause of Hermansky-Pudlak syndrome type 2 (HPS2) [MIM:608233]. Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous, rare, autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS. HPS2 differs from the other forms of HPS in that it includes immunodeficiency in its phenotype and patients with HPS2 have an increased susceptibility to infections.
Q9Z1T1	Defects in Ap3b1 are the cause of the autosomal recessive phenotype 'pearl' (pe). Pearl mice exhibit hypopigmentation, lysosomal secretion abnormalities, and platelet-dense granules with reduced levels of adenine nucleotides and serotonin. The changes in platelets lead to prolonged bleeding. Additionally, pearl mice exhibit reduced sensitivity in the dark-adapted state.
P25054	Defects in APC are a cause of familial adenomatous polyposis (FAP) [MIM:175100]; which includes also Gardner syndrome (GS). FAP and GS contribute to tumor development in patients with uninherited forms of colorectal cancer. FAP is characterized by adenomatous polyps of the colon and rectum, but also of upper gastrointestinal tract (ampullary, duodenal and gastric adenomas). This is a viciously premalignant disease with one or more polyps progressing through dysplasia to malignancy in untreated gene carriers with a median age at diagnosis of 40 years.
P25054	Defects in APC are a cause of hereditary desmoid disease (HDD) [MIM:135290]; also known as familial infiltrative fibromatosis (FIF). HDD is an autosomal dominant trait with 100% penetrance and possible variable expression among affected relatives. HDD patients show multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Desmoid tumors appears also as a complication of familial adenomatous polyposis.
P25054	Defects in APC are a cause of medulloblastoma (MDB) [MIM:155255]. MDB is a malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. Although the majority of medulloblastomas occur sporadically, some manifest within familial cancer syndromes such as Turcot syndrome and basal cell nevus syndrome (Gorlin syndrome).
P25054	Defects in APC are a cause of mismatch repair cancer syndrome (MMRCS) [MIM:276300]; also known as Turcot syndrome or brain tumor-polyposis syndrome 1 (BTPS1). MMRCS is an autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots.
P02647	Defects in APOA1 are a cause of high density lipoprotein deficiency type 2 (HDLD2) [MIM:604091]; also known as familial hypoalphalipoproteinemia (FHA). Inheritance is autosomal dominant.
P02647	Defects in APOA1 are a cause of the low HDL levels observed in high density lipoprotein deficiency type 1 (HDLD1) [MIM:205400]; also known as analphalipoproteinemia or Tangier disease (TGD). HDLD1 is a recessive disorder characterized by the absence of plasma HDL, accumulation of cholesteryl esters, premature coronary artery disease, hepatosplenomegaly, recurrent peripheral neuropathy and progressive muscle wasting and weakness. In HDLD1 patients, ApoA-I fails to associate with HDL probably because of the faulty conversion of pro-ApoA-I molecules into mature chains, either due to a defect in the converting enzyme activity or a specific structural defect in Tangier ApoA-I.
P02647	Defects in APOA1 are the cause of amyloid polyneuropathy- nephropathy Iowa type (AMYLIOWA) [MIM:107680]; also known as amyloidosis van Allen type or familial amyloid polyneuropathy type III. AMYLIOWA is a hereditary generalized amyloidosis due to deposition of amyloid mainly constituted by apolipoprotein A1. The clinical picture is dominated by neuropathy in the early stages of the disease and nephropathy late in the course. Death is due in most cases to renal amyloidosis. Severe peptic ulcer disease can occurr in some and hearing loss is frequent. Cataracts is present in several, but vitreous opacities are not observed.
P02647	Defects in APOA1 are a cause of amyloidosis type 8 (AMYL8) [MIM:105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.
P09813	Defects in Apoa2 are the cause of senescence accelerated mouse (SAM), the senile amyloid is a mutated apolipoprotein A-II.
Q6Q788	Defects in APOA5 are a cause of susceptibility to familial hypertriglyceridemia [MIM:145750]. It is a coronary heart disease risk factor. On a regular diet the patient demonstrates increased plasma VLDL. Plasma triglycerides are persistently increased, while plasma cholesterol and phospholipids are usually within normal limits.
Q6Q788	Defects in APOA5 are a cause of hyperlipoproteinemia type 5 [MIM:144650]. Hyperlipoproteinemia type 5 is characterized by increased amounts of chylomicrons and very low density lipoprotein (VLDL) and decreased low density lipoprotein (LDL) and high density lipoprotein (HDL) in the plasma after a fast. Numerous conditions cause this phenotype, including insulin-dependent diabetes mellitus, contraceptive steroids, alcohol abuse, and glycogen storage disease type 1A (GSD1A) [MIM:232200].
P14417	Elevated plasma concentrations of apo(a) and its naturally occurring proteolytic fragments are correlated with atherosclerosis. Homology with plasminogen kringles IV and V is thought to underlie the atherogenicity of the protein, because the fragments are competing with plasminogen for fibrin(ogen) binding.
Q13787	Defects in APOB are a cause of familial hypobetalipoproteinemia (FHBL) [MIM:107730]. FHBL is a genetically heterogeneous autosomal co-dominant disorder, associated with reduced plasma concentrations of apoB, LDL and VLDL. Heterozygotes for FHBL are usually asymptomatic with LDL cholesterol and apoB- 100 concentrations less than 50% of those in normal plasma. Homozygotes have extremely low plasma LDL cholesterol and apoB-100 concentrations, and clinical presentation may vary from no symptoms to severe gastrointestinal and neurological dysfunction similar to abetalipoproteinemia [MIM:200100].
Q13787	Defects in APOB are a cause of familial ligand-defective apolipoprotein B-100 (FDB) [MIM:144010]. FDB is a dominantly inherited disorder of lipoprotein metabolism leading to hypercholesterolemia and increased proneness to coronary artery disease (CAD). The plasma cholesterol levels are dramatically elevated due to impaired clearance of LDL particles by defective APOB/E receptors.
Q13787	Defects in APOB associated with defects in other genes (polygenic) can contribute to hypocholesterolemia.
P02655	Defects in APOC2 are the cause of hyperlipoproteinemia type 1B [MIM:207750]. It is an autosomal recessive trait characterized by hypertriglyceridemia, xanthomas, and increased risk of pancreatitis and early atherosclerosis.
P02656	Defects in APOC3 may be a cause of hyperalphalipoproteinemia [MIM:143470]. Affected individuals show high levels of alpha-lipoprotein (high density lipoprotein/HDL).
P02649	Defects in APOE are a cause of hyperlipoproteinemia type 3 [MIM:107741]; also known as familial dysbetalipoproteinemia. Individuals with hyperlipoproteinemia type 3, are clinically characterized by xanthomas, yellowish lipid deposits in the palmar crease, or less specific on tendons and on elbows. The disorder rarely manifests before the third decade in men. In women, it is usually expressed only after the menopause. The vast majority of the patients are homozygous for APOE*2 alleles. More severe cases of hyperlipoproteinemia type 3 have also been observed in individuals heterozygous for rare APOE variants. The influence of APOE on lipid levels is often suggested to have major implications for the risk of coronary artery disease (CAD). Individuals carrying the common APOE*4 variant are at higher risk of CAD.
P02649	The APOE*4 allele is associated with late onset Alzheimer disease 2 (AD2) [MIM:104310]. The APOE*4 allele is genetically associated with the common late onset familial and sporadic forms of Alzheimer disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE*4 alleles in 42 families with late onset AD. Thus APOE*4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE*4 was virtually sufficient to cause AD by age 80. The mechanism by which APOE*4 participates in pathogenesis is not known.
P02649	Defects in APOE are a cause of sea-blue histiocyte disease [MIM:269600]; also known as sea-blue histiocytosis. This disorder is characterized by splenomegaly, mild thrombocytopenia and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses.
P02649	Defects in APOE are a cause of lipoprotein glomerulopathy (LPG) [MIM:611771]. LPG is an uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. It mainly affects people of Japanese and Chinese origin. The disorder has rarely been described in Caucasians.
Q7Z6V7	Defects in APTX are the cause of ataxia-oculomotor apraxia syndrome (AOA) [MIM:208920]. AOA is an autosomal recessive syndrome characterized by early-onset cerebellar ataxia, oculomotor apraxia, early areflexia and late peripheral neuropathy.
Q7Z6V7	Defects in APTX are a cause of coenzyme Q10 deficiency [MIM:607426]. Coenzyme Q10 deficiency is an autosomal recessive disorder with variable manifestations. It can be associated with three main clinical phenotypes: a predominantly myopathic form with central nervous system involvement, an infantile encephalomyopathy with renal dysfunction and an ataxic form with cerebellar atrophy. Coenzyme Q10 deficiency due to APTX mutations is typically associated with cerebellar ataxia.
P07741	Defects in APRT are the cause of APRT deficiency [MIM:102600]; also known as 2,8-dihydroxyadenine urolithiasis. It is an autosomal recessive disease characterized by renal failure. Patients have 2,8-dihydroxyadenine (DHA) urinary stones.
P41181	Defects in AQP2 are the cause of diabetes insipidus nephrogenic autosomal (ANDI) [MIM:125800]; also known as diabetes insipidus nephrogenic type 2. ANDI is caused by the inability of the renal collecting ducts to absorb water in response to arginine vasopressin. It is characterized by excessive water drinking (polydypsia), excessive urine excretion (polyuria), persistent hypotonic urine, and hypokalemia. Inheritance can be autosomal dominant or recessive.
Q3SXY8	Defects in ARL13B are the cause of Joubert syndrome type 8 (JBTS8) [MIM:612291]. JBTS is an autosomal recessive disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermis hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease.
P05089	Defects in ARG1 are the cause of argininemia (ARGIN) [MIM:207800]; also known as hyperargininemia. Argininemia is a rare autosomal recessive disorder of the urea cycle. Arginine is elevated in the blood and cerebrospinal fluid, and periodic hyperammonemia occurs. Clinical manifestations include developmental delay, seizures, mental retardation, hypotonia, ataxia, progressive spastic quadriplegia.
Q15052	Defects in ARHGEF6 are the cause of mental retardation X- linked type 46 (MRX46) [MIM:300436]. Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non- syndromic mental retardation patients do not manifest other clinical signs.
O43307	Defects in ARHGEF9 are a cause of startle disease with epilepsy (STHEE) [MIM:300607]; also known as hyperekplexia with epilepsy. Startle disease is a genetically heterogeneous neurologic disorder. STHE is characterized by muscular rigidity of central nervous system origin, particularly in the neonatal period, and by an exaggerated startle response to unexpected acoustic or tactile stimuli.
O15013	Defects in ARHGEF10 are the cause of slowed nerve conduction velocity (SNCV) [MIM:608236]. Affected individuals present a reduction in nerve conduction velocities without any clinical signs of peripheral or central nervous system dysfunction. SNCV inheritance is autosomal dominant.
Q9NZN5	A chromosomal aberration involving ARHGEF12 may be a cause of acute leukemia. Translocation t(11;11)(q23;23) with MLL.
Q5SW96	Defects in LDLRAP1 are the cause of autosomal recessive hypercholesterolemia (ARH) [MIM:603813]. ARH is a disorder caused by defective internalization of LDL receptors (LDLR) in the liver. ARH has the clinical features of familial hypercholesterolemia (FH) [MIM:143890] homozygotes, including severely elevated plasma LDL cholesterol, tuberous and tendon xanthomata, and premature atherosclerosis. LDL receptor (LDLR) activity measured in skin fibroblasts is normal, as the LDL binding ability.
Q969Q4	Defects in ARL11 may be a cause of susceptibility to chronic lymphocytic leukemia (CLL) [MIM:151400].
Q9H0F7	Defects in ARL6 are a cause of Bardet-Biedl syndrome type 3 (BBS3) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease.
P04424	Defects in ASL are the cause of arginosuccinicaciduria (ARGINSA) [MIM:207900]. Arginosuccinicaciduria is an autosomal recessive disorder of the urea cycle. The disease is characterized by mental and physical retardation, liver enlargement, skin lesions, dry and brittle hair showing trichorrhexis nodosa microscopically and fluorescing red, convulsions, and episodic unconsciousness.
P0C7Q2	Defects in ARMS2 influence susceptibility to age-related macular degeneration type 8 (ARMD8) [MIM:611313]. ARMD is the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch's membrane. ARMD is likely to be a mechanistically heterogeneous group of disorders, and the specific disease mechanisms that underlie the vast majority of cases are currently unknown. However, a number of studies have suggested that both genetic and environmental factors are likely to play a role.
P08168	S-antigen induces autoimmune uveitis.
Q28281	S-antigen induces autoimmune uveitis.
Q28281	Defects in SAG may be the cause of generalized progressive retinal atrophy (gPRA) in some breeds.
P10523	Defects in SAG are a cause of congenital stationary night blindness Oguchi type (CSNBO) [MIM:258100]; also known as Oguchi disease. Congenital stationary night blindness is a non- progressive retinal disorder characterized by impaired night vision. CSNBO is an autosomal recessive form associated with fundus discoloration and abnormally slow dark adaptation.
P20443	S-antigen induces autoimmune uveitis.
P79260	S-antigen induces autoimmune uveitis.
P15887	S-antigen induces autoimmune uveitis.
P15289	Defects in ARSA are a cause of leukodystrophy metachromatic (MLD) [MIM:250100]. MLD is a disease due to a lysosomal storage defect. It is characterized by intralysosomal storage of cerebroside-3-sulfate in neural and non-neural tissues, with a diffuse loss of myelin in the central nervous system. Progressive demyelination causes a variety of neurological symptoms, including gait disturbances, ataxias, optical atrophy, dementia, seizures, and spastic tetraparesis. Three forms of the disease can be distinguished according to the age at onset: late- infantile, juvenile and adult.
P15289	Arylsulfatase A activity is defective in multiple sulfatase deficiency (MSD) [MIM:272200]. MSD is a disorder characterized by decreased activity of all known sulfatases. MSD is due to defects in SUMF1 resulting in the lack of post- translational modification of a highly conserved cysteine into 3- oxoalanine. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay.
P33727	Defects in ARSB are the cause of mucopolysaccharidosis type VI (MPS-VI). MPS-VI has been described in Siamese cats.
P15848	Defects in ARSB are the cause of mucopolysaccharidosis type 6 (MPS6) [MIM:253200]; also known as Maroteaux-Lamy syndrome. MPS6 is an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of dermatan sulfate. Clinical features can include abnormal growth, short stature, stiff joints, skeletal malformations, corneal clouding, hepatosplenomegaly, and cardiac abnormalities. A wide variation in clinical severity is observed.
P15848	Arylsulfatase B activity is defective in multiple sulfatase deficiency (MSD) [MIM:272200]. MSD is a disorder characterized by decreased activity of all known sulfatases. MSD is due to defects in SUMF1 resulting in the lack of post- translational modification of a highly conserved cysteine into 3- oxoalanine. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay.
P50430	Defects in Arsb are the cause of mucopolysaccharidosis type VI (MPS-VI).
P51690	Defects in ARSE are the cause of chondrodysplasia punctata X-linked recessive type 1 (CDPX1) [MIM:302950]. CDP is a clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. CDPX1 is a congenital defect of bone and cartilage development characterized by aberrant bone mineralization, severe underdevelopment of nasal cartilage, and distal phalangeal hypoplasia. This disease can also be induced by inhibition with the drug warfarin.
Q96QS3	Defects in ARX are the cause of lissencephaly X-linked type 2 (LISX2) [MIM:300215]; also known as lissencephaly X-linked with ambiguous genitalia (XLAG). LISX2 is a classic type lissencephaly associated with abnormal genitalia. LISX2 patients have severe congenital or postnatal microcephaly, lissencephaly, agenesis of the corpus callosum, neonatal-onset intractable epilepsy, poor temperature regulation, chronic diarrhea, and ambiguous or underdeveloped genitalia.
Q96QS3	Defects in ARX are the cause of epileptic encephalopathy early infantile type 1 (EIEE1) [MIM:308350]; also known as myoclonic epilepsy X-linked with intellectual disability and spasticity, X-linked West syndrome or X-linked infantile spasm syndrome (ISSX). EIEE1 is a severe form of epilepsy characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Patients may progress to West syndrome, which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG.
Q96QS3	Defects in ARX are a cause of Partington syndrome (PRTS) [MIM:309510]; also known as X-linked syndromic mental retardation 1 (MRXS1). PRTS is characterized by mental retardation, episodic dystonic hand movements, and dysarthria.
Q96QS3	Defects in ARX are the cause of mental retardation X- linked ARX-related (MRXARX) [MIM:300419]. Mental retardation is a mental disorder characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.
Q96QS3	Defects in ARX are the cause of agenesis of the corpus callosum with abnormal genitalia (ACCAG) [MIM:300004]. A X-linked syndrome with variable expression in females. It is characterized by agenesis of corpus callosum, mental retardation and seizures. Manifestations in surviving males include severe acquired micrencephaly, mental retardation, limb contractures, scoliosis, tapered fingers with hyperconvex nails, a characteristic face with large eyes, prominent supraorbital ridges, synophrys, optic atrophy, broad alveolar ridges, and seizures. Urologic anomalies include renal dysplasia, cryptorchidism, and hypospadias.
Q96KY8	Genetic variations in NAT2 determine N-acetylation polymorphism by a low or high NAT activity in the liver [MIM:243400]. It has been implicated in the action and toxicity of amine-containing drugs, and in the susceptibility to bladder cancer and systemic lupus erythematosus. This isozyme is responsible for this polymorphism.
Q13510	Defects in ASAH1 are the cause of Farber disease (FD) [MIM:228000]; also known as Farber lipogranulomatosis. This sphingolipid disease is characterized by subcutaneous lipid-loaded nodules, excruciating pain in the joints and extremities, marked accumulation of ceramide in lysosomes, and death by three years of age.
P17405	Defects in SMPD1 are the cause of Niemann-Pick disease type A (NPDA) [MIM:257200]; also known as Niemann-Pick disease classical infantile form. It is an early-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Niemann-Pick disease type A is a primarily neurodegenerative disorder characterized by onset within the first year of life, mental retardation, digestive disorders, failure to thrive, major hepatosplenomegaly, and severe neurologic symptoms. The severe neurological disorders and pulmonary infections lead to an early death, often around the age of four. Clinical features are variable. A phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B.
P17405	Defects in SMPD1 are the cause of Niemann-Pick disease type B (NPDB) [MIM:607616]; also known as Niemann-Pick disease visceral form. It is a late-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Clinical signs involve only visceral organs. The most constant sign is hepatosplenomegaly which can be associated with pulmonary symptoms. Patients remain free of neurologic manifestations. However, a phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. In Niemann-Pick disease type B, onset of the first symptoms occurs in early childhood and patients can survive into adulthood.
Q9BZE9	Chromosomal aberrations involving ASPSCR1 are recurrent in alveolar soft part sarcoma (ASPS) [MIM:606243]. Translocation t(X;17)(p11;q25) with TFE3 forms a ASPSCR1-TFE3 fusion protein.
Q9BZE9	A chromosomal aberration involving ASPSCR1 may be a cause of papillary renal cell carcinoma (PRCC) [MIM:605074].
P20933	Defects in AGA are the cause of aspartylglucosaminuria (AGU) [MIM:208400]. AGU is an inborn lysosomal storage disease. Clinical features of AGU include mild to severe mental retardation manifesting from the age of 2, coarse facial features and mild connective tissue abnormalities. This recessively inherited disease is overrepresented in the Finnish population.
Q9NVS1	Defects in ASPM are the cause of microcephaly primary type 5 (MCPH5) [MIM:608716]; also known as true microcephaly or microcephaly vera. Microcephaly is defined as a head circumference more than 3 standard deviations below the age-related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits. This entity is inherited as autosomal recessive trait.
Q9BXN1	Variation in the poly-Asp region of ASPN is associated with osteoarthritis susceptibility type 3 (OS3) [MIM:607850]; also known as osteoarthritis of knee/hip. Osteoarthritis is a common disease that produces joint pain and stiffness together with radiologic evidence of progressive degeneration of joint cartilage. ASPN allele having 14 aspartic acid repeats in the N- terminal region of the protein (D14), is overrepresented relative to the common allele having 13 aspartic acid repeats (D13). The frequency of the D14 allele increases with disease severity. The D14 allele is also overrepresented in individuals with hip osteoarthritis.
P14568	Defects in ASS1 are the cause of a bovine form of citrullinemia.
P00966	Defects in ASS1 are the cause of citrullinemia type 1 (CTLN1) [MIM:215700]. Citrullinemia belongs to the urea cycle disorders. It is an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. CTLN1 usually manifests in the first few days of life. Affected infants appear normal at birth, but as ammonia builds up in the body they present symptoms such as lethargy, poor feeding, vomiting, seizures and loss of consciousness. Less commonly, a milder CTLN1 form can develop later in childhood or adulthood.
Q76L83	A chromosomal aberration involving ASXL2 is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with MYST3 generates a MYST3-ASXL2 fusion protein.
O60312	Defects in ATP10A are a cause of Angelman syndrome (AS) [MIM:105830]; also known as 'happy puppet syndrome'. AS is characterized by features of severe motor and intellectual retardation, microcephaly, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, hyperactivity, hypopigmentation, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, and an unusual facies characterized by macrostomia, a large mandible and open-mouthed expression, a great propensity for protruding the tongue ('tongue thrusting'), and an occipital groove.
Q9NQ11	Defects in ATP13A2 are the cause of Kufor-Rakeb syndrome (KRS) [MIM:606693]; also known as Parkinson disease type 9 (PARK9). KRS is a rare hereditary disease with juvenile onset. In addition to typical signs of Parkinson disease, affected individuals show symptoms of more widespread neurodegeneration, including dementia.
Q4VNC1	A chromosomal aberration involving ATP13A4 is found in 2 patients with specific language impairment (SLI) disorders. Paracentric inversion inv(3)(q25;q29). The inversion produces a disruption of the protein.
P50993	Defects in ATP1A2 are the cause of familial hemiplegic migraine type 2 (FHM2) [MIM:602481]. FHM2 is a rare, severe, autosomal dominant subtype of migraine characterized by aura and some hemiparesis.
P50993	Defects in ATP1A2 are a cause of alternating hemiplegia of childhood (AHC) [MIM:104290]. AHC is typically distinguished from familial hemiplegic migraine by infantile onset of the symptoms and high prevalence of associated neurological deficits that become increasingly obvious with age.
P13637	Defects in ATP1A3 are the cause of dystonia type 12 (DYT12) [MIM:128235]; also known as rapid-onset dystonia parkinsonism (RDP). DYT12 is an autosomal dominant dystonia- parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT12 patients develop dystonia and parkinsonism between 15 and 45 years of age. The disease is characterized by an unusually rapid evolution of signs and symptoms. The sudden onset of symptoms over hours to a few weeks, often associated with physical or emotional stress, suggests a trigger initiating a nervous system insult resulting in permanent neurologic disability.
O14983	Defects in ATP2A1 are the cause of Brody myopathy (BRM) [MIM:601003]. An autosomal recessive myopathy characterized by increasing impairment of relaxation of fast twist skeletal muscle during exercise.
P16615	Defects in ATP2A2 are a cause of acrokeratosis verruciformis (AKV) [MIM:101900]; also known as Hopf disease. AKV is a localized disorder of keratinization, which is inherited as an autosomal dominant trait. Its onset is early in life with multiple flat-topped, flesh-colored papules on the hands and feet, punctate keratoses on the palms and soles, with varying degrees of nail involvement. The histopathology shows a distinctive pattern of epidermal features with hyperkeratosis, hypergranulosis, and acanthosis together with papillomatosis. These changes are frequently associated with circumscribed elevations of the epidermis that are said to resemble church spires. There are no features of dyskeratosis or acantholysis, the typical findings in lesions of Darier disease.
P16615	Defects in ATP2A2 are the cause of Darier disease (DD) [MIM:124200]; also known as Darier-White disease (DAR). DD is an autosomal dominantly inherited skin disorder characterized by loss of adhesion between epidermal cells (acantholysis) and abnormal keratinization. Patients with mild disease may have no more than a few scattered keratotic papules or subtle nail changes, whereas those with severe disease are handicapped by widespread malodorous keratotic plaques. In a few families, neuropsychiatric abnormalities such as mild mental retardation, schizophrenia, bipolar disorder and epilepsy have been reported. Stress, UV exposure, heat, sweat, friction, and oral contraception exacerbate disease symptoms. Prevalence has been estimated at 1 in 50000.
Q9R0K7	Atp2b2 null deficient mice are deaf.
P98194	Defects in ATP2C1 are the cause of Hailey-Hailey disease (HHD) [MIM:169600]; also known as benign familial pemphigus. HHD is an autosomal dominant disorder characterized by persistent blisters and suprabasal cell separation (acantholysis) of the epidermis, due to impaired keratinocyte adhesion. Patients lacking all isoforms except isoform 2 have HHD.
P32876	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P48202	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
A1XQS5	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q06645	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P17605	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P07926	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P56383	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q5RAP9	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q06646	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q06056	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q3ZC75	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
P56384	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q5RFL2	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
Q71S46	This protein is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
O43520	Defects in ATP8B1 are the cause of progressive familial intrahepatic cholestasis type 1 (PFIC1) [MIM:211600]; also known as Byler disease. PFIC1 is an autosomal recessive disorder, characterized by early infancy cholestasis, that may be initially episodic but progresses to malnutrition, growth retardation and end-stage liver disease before adulthood.
O43520	Defects in ATP8B1 are the cause of benign recurrent intrahepatic cholestasis type 1 (BRIC1) [MIM:243300]; also known as Summerskill syndrome. BRIC is characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically.
O43520	Defects in ATP8B1 can be associated with intrahepatic cholestasis of pregnancy (ICP) [MIM:147480]; also known as pregnancy-related cholestasis. ICP is a multifactorial liver disorder of pregnancy. It presents during the second or, more commonly, the third trimestre of pregnancy with intense pruritus which becomes more severe with advancing gestation and cholestasis. Cholestasis results from abnormal biliary transport from the liver into the small intestine. ICP causes fetal distress, spontaneous premature delivery and intrauterine death. ICP patients have spontaneous and progressive disappearance of cholestasis after delivery.
Q86WG3	Defects in ATCAY are the cause of cerebellar ataxia, cayman type (ATCAY) [MIM:601238]. ATCAY is found in a population isolate on Grand Cayman Island and causes a marked psychomotor retardation and prominent nonprogressive cerebellar dysfunction including nystagmus, intention tremor, dysarthria, and wide-based ataxic gait. Hypotonia is present from early childhood.
Q8BHE3	Defects in Atcay are the cause of jittery phenotype, which is characterized by severe truncal and limb ataxia and die of starvation and dehydration by 3-4 weeks of age.
P18846	A chromosomal aberration involving ATF1 is associated with angiomatoid fibrous histiocytoma (AFH) [MIM:612160]. Translocation t(12;16)(q13;p11.2) with FUS generates a chimeric ATF1/FUS protein.
P18846	A chromosomal aberration involving ATF1 is associated with angiomatoid fibrous histiocytoma (AFH) [MIM:612160]. Translocation t(12;22)(q13;q12) with EWSR1 generates a chimeric ATF1/EWSR1 protein.
Q86TH1	Defects in ADAMTSL2 are the cause of geleophysic dysplasia [MIM:231050]. Geleophysic dysplasia is an autosomal recessive disorder characterized by short stature, brachydactyly, thick skin and cardiac valvular anomalies often responsible for an early death.
Q6UY14	Defects in ADAMTSL4 are a cause of autosomal recessive isolated ectopia lentis (EL) [MIM:225100]. EL is a rare condition characterized by partial or complete displacement of the lens from its space resulting from defective zonule formation.
Q8WXF7	Defects in ATL1 are the cause of spastic paraplegia autosomal dominant type 3 (SPG3) [MIM:182600]; also known as Strumpell-Lorrain syndrome. Spastic paraplegia is a degenerative spinal cord disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs.
Q13315	Defects in ATM are the cause of ataxia telangiectasia (AT) [MIM:208900]; also known as Louis-Bar syndrome, which includes four complementation groups: A, C, D and E. This rare recessive disorder is characterized by progressive cerebellar ataxia, dilation of the blood vessels in the conjunctiva and eyeballs, immunodeficiency, growth retardation and sexual immaturity. AT patients have a strong predisposition to cancer; about 30% of patients develop tumors, particularly lymphomas and leukemias. Cells from affected individuals are highly sensitive to damage by ionizing radiation and resistant to inhibition of DNA synthesis following irradiation.
Q13315	Defects in ATM contribute to T-cell acute lymphoblastic leukemia (TALL) and T-prolymphocytic leukemia (TPLL). TPLL is characterized by a high white blood cell count, with a predominance of prolymphocytes, marked splenomegaly, lymphadenopathy, skin lesions and serous effusion. The clinical course is highly aggressive, with poor response to chemotherapy and short survival time. TPLL occurs both in adults as a sporadic disease and in younger AT patients.
Q13315	Defects in ATM contribute to B-cell non-Hodgkin lymphomas (BNHL), including mantle cell lymphoma (MCL).
Q13315	Defects in ATM contribute to B-cell chronic lymphocytic leukemia (BCLL). BCLL is the commonest form of leukemia in the elderly. It is characterized by the accumulation of mature CD5+ B lymphocytes, lymphadenopathy, immunodeficiency and bone marrow failure.
Q62388	Atm-deficient mice show a phenotype similar to human ataxia telangiectasia (AT) and consistently develop immature T- cells malignancies.
P54259	Defects in ATN1 are the cause of dentatorubral- pallidoluysian atrophy (DRPLA) [MIM:125370]. DRPLA is an autosomal dominant neurodegenerative disorder characterized by a loss of neurons in the dentate nucleus, rubrum, glogus pallidus and Luys'body. Clinical features are myoclonus epilepsy, dementia, and cerebellar ataxia. Onset of the disease occurs usually in the second decade of life and death in the fourth.
P54710	Defects in FXYD2 are the cause of hypomagnesemia type 2 (HOMG2) [MIM:154020]; also known as dominant renal hypomagnesemia or hypomagnesemia with hypocalciuria. HOMG2 is a disorder due to primary renal wasting of magnesium. Plasma levels of other electrolytes are normal. The only abnormality found, in addition to low magnesium levels, is lowered renal excretion of calcium resulting in hypocalciuria.
P18434	Parietal cell autoantigen associated with autoimmune gastritis.
Q8HNQ4	Defects in MT-ATP6 are the cause of neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) [MIM:551500].
Q8HNQ4	Defects in MT-ATP6 are a cause of Leber hereditary optic neuropathy (LHON) [MIM:535000]. LHON is a maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
Q8HNQ4	Defects in MT-ATP6 are a cause of Leigh syndrome (LS) [MIM:256000]. LS is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions.
Q8HNQ4	Defects in MT-ATP6 are a cause of infantile bilateral striatal necrosis [MIM:500003]. Bilateral striatal necrosis is a neurological disorder resembling Leigh syndrome.
Q04656	Defects in ATP7A are the cause of Menkes disease (MNKD) [MIM:309400]; also known as kinky hair disease. MNKD is an X- linked recessive disorder of copper metabolism characterized by generalized copper deficiency. MNKD results in progressive neurodegeneration and connective-tissue disturbances: focal cerebral and cerebellar degeneration, early growth retardation, peculiar hair, hypopigmentation, cutis laxa, vascular complications and death in early childhood. The clinical features result from the dysfunction of several copper-dependent enzymes.
Q04656	Defects in ATP7A are the cause of occipital horn syndrome (OHS) [MIM:304150]; also known as X-linked cutis laxa. OHS is an X-linked recessive disorder of copper metabolism. Common features are unusual facial appearance, skeletal abnormalities, chronic diarrhea and genitourinary defects. The skeletal abnormalities included occipital horns, short, broad clavicles, deformed radii, ulnae and humeri, narrowing of the rib cage, undercalcified long bones with thin cortical walls and coxa valga.
Q64430	Defects in Atp7a are associated with mottled, an X-linked recessive condition characterized by mottled pigmentation of the coat, defects in connective tissue and neonatal or fetal death. It is due to a defect in absorption and transport of copper. The mottled mutants exhibit a diversity of phenotypes. Two of these mutants are called brindled and blotchy and their phenotypes resemble classical Menkes disease (MD) and occipital horn syndrome (OHS) in humans, respectively. Other mutants are called dappled, mosaic, tortoiseshell, pewter, etc.
P35670	Defects in ATP7B are the cause of Wilson disease (WD) [MIM:277900]. WD is an autosomal recessive disorder of copper metabolism in which copper cannot be incorporated into ceruloplasmin in liver, and cannot be excreted from the liver into the bile. Copper accumulates in the liver and subsequently in the brain and kidney. The disease is characterized by neurologic manifestations and signs of cirrhosis.
Q64446	Defects in Atp7b are the cause of the toxic milk mouse mutant (tx) phenotype, characterized by accumulation of copper in the liver in a manner similar to that observed in patients with Wilson disease.
Q64535	Deficiency of Atp7b expression is the cause of the Long- Evans Cinnamon (LEC) phenotype, inherited in an autosomal recessive manner, characterized by excessive hepatic copper accumulation, defective holoceruloplasmin biosynthesis, impaired biliary copper excretion and the development of necrotizing hepatitis by 4 months of age.
Q8N5M1	Defects in ATPAF2 are the cause of complex V mitochondrial respiratory chain ATPAF2 subunit deficiency (ATPAF2 deficiency) [MIM:604273]; also known as ATP synthase deficiency or ATPase deficiency. ATPAF2 deficiency seems to be an early presenting disease in which lactic acidosis, dysmorphic features, and methyl glutaconic aciduria can be major clues in the diagnosis. Dysmorphic features include a large mouth, prominent nasal bridge, micrognathia, rocker-bottom feet and flexion contractures of the limbs associated with camptodactyly. Patients are hypertonic and have an enlarged liver, hypoplastic kidneys and elevated lactate levels in urine, plasma and cerebro spinal fluid (CSF).
Q99J86	Defects in Atrn (isoform 1) are the cause of the autosomal recessive phenotype zitter (zi), which is characterized by progressive hypomyelination and vacuolation in the central nervous system resulting in early-onset tremor and progressive flaccid paresis of the hind limb. This is due to an 8-bp deletion at the splice donor site of intron 12, which results in aberrant and unstable transcripts.
Q9H0Z1	Defects in ATRX are the cause of alpha-thalassemia mental retardation syndrome X-linked non-deletion type (ATRX) [MIM:301040]. ATR-X is an X-linked disorder comprising severe psychomotor retardation, facial dysmorphism, urogenital abnormalities, and alpha-thalassemia. An essential phenotypic trait are hemoglobin H erythrocyte inclusions.
Q9H0Z1	Defects in ATRX are the cause of mental retardation syndromic X-linked with hypotonic facies syndrome type 1 (MRXSHF1) [MIM:309580]; also called Carpenter-Waziri syndrome (CWS), Juberg- Marsidi syndrome (JMS), Smith-Fineman-Myers syndrome type 1 (SFM1). Clinical features include severe mental retardation, dysmorphic facies, and a highly skewed X-inactivation pattern in carrier women. Other more variable features include hypogonadism, deafness, renal anomalies, and mild skeletal defects.
Q9H0Z1	Defects in ATRX are a cause of alpha-thalassemia myelodysplasia syndrome (ATMDS) [MIM:300448]. In this disorder, alpha-thalassemia occurs as an acquired abnormality in association with a multilineage myelodysplasia.
Q13535	Defects in ATR are a cause of Seckel syndrome type 1 (SCKL1) [MIM:210600]. SCKL1 is a rare autosomal recessive disorder characterized by growth retardation, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance.
Q9H324	Defects in ADAMTS10 are the cause of Weill-Marchesani syndrome autosomal recessive (ARWMS) [MIM:277600]. ARWMS is a rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities including microspherophakia, ectopia lentis, severe myopia and glaucoma.
Q76LX8	Defects in ADAMTS13 are the cause of congenital thrombotic thrombocytopenic purpura (TTP) [MIM:274150]; also known as Upshaw-Schulman syndrome (USS). Congenital TTP is a life- threatening systemic disorder due to constitutional deficiency of vWF-cleaving protease. Typical features are hemolytic anemia with fragmentation of erythrocytes, thrombocytopenia, diffuse and nonfocal neurologic findings, decreased renal function and fever. Congenital TTP is characterized by neonatal onset, response to fresh plasma infusion and frequent relapses. Inheritance pattern is autosomal recessive. In sporadic cases, TTP is associated with deficiency of vWF-cleaving protease due to the presence of inhibiting autoantibodies (acquired TTP or autoimmune TTP). Acquired TTP is characterized by adult-onset. TTP shares overlapping clinical features with hemolytic-uremic syndrome (HUS) [MIM:235400], a disease characterized by acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia associated with distorted erythrocytes.
P59511	Defects in Adamts20 are the cause of the belted (bt) phenotype. It is a pigmental defect which occurs as a result of a defect in melanocyte development.
P79331	Defects in ADAMTS2 are the cause of dermatosparaxis, a recessively inherited disorder characterized by severe skin fragility and biochemically by the presence in skin of procollagen incompletely processed at the N-terminus.
O95450	Defects in ADAMTS2 are the cause of Ehlers-Danlos syndrome type 7C (EDS7C) [MIM:225410]. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS7C is marked by extremely fragile tissues, hyperextensible skin and easy bruising. Facial skin contains numerous folds, as in the cutis laxa syndrome.
P17735	Defects in TAT are the cause of tyrosinemia type 2 (TYRO2) [MIM:276600]; also known as Richner-Hanhart syndrome. TYRO2 is an inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and oculocutaneous manifestations. Typical features include palmoplantar keratosis, painful corneal ulcers, and mental retardation.
Q9UBB4	Defects in ATXN10 are the cause of spinocerebellar ataxia type 10 (SCA10) [MIM:603516]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA10 is an autosomal dominant cerebellar ataxia (ADCA).
P54253	Defects in ATXN1 are the cause of spinocerebellar ataxia type 1 (SCA1) [MIM:164400]; also known as olivopontocerebellar atrophy I (OPCA I or OPCA1). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA1 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. SCA1 is caused by expansion of a CAG repeat in the coding region of ATXN1. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
Q99700	Defects in ATXN2 are the cause of spinocerebellar ataxia type 2 (SCA2) [MIM:183090]; also known as olivopontocerebellar atrophy II (OPCA II or OPCA2). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA2 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. SCA2 is characterized by hyporeflexia, myoclonus and action tremor and dopamine-responsive parkinsonism. SCA2 is caused by expansion of a CAG repeat in the coding region of ATXN2. Longer expansions result in earlier onset of the disease. In some patients with smaller CAG repeat expansions, SCA2 presents as pure familial parkinsonism without cerebellar signs.
Q9H3N0	Defects in ATXN3 are the cause of spinocerebellar ataxia type 3 (SCA3) [MIM:109150]; also known as Machado-Joseph disease (MJD). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA3 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. The molecular defect in SCA3 is the a CAG repeat expansion in ATXN3 coding region. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
O15265	Defects in ATXN7 are the cause of spinocerebellar ataxia type 7 (SCA7) [MIM:164500]; also known as olivopontocerebellar atrophy III (OPCA III or OPCA3) or olivopontocerebellar atrophy with retinal degeneration. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA7 belongs to the autosomal dominant cerebellar ataxias type II (ADCA II) which are characterized by cerebellar ataxia with retinal degeneration and pigmentary macular dystrophy.
Q156A1	Defects in ATXN8 are the cause of spinocerebellar ataxia type 8 (SCA8) [MIM:608768]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA8 is an autosomal dominant cerebellar ataxia (ADCA). It is caused by a CAG repeat expansion in ATXN8, which is translated into a nearly pure polyglutamine protein which forms 1C2-positive inclusions in Purkinje cells and other neurons.
Q13825	Defects in AUH are the cause of 3-methylglutaconic aciduria type 1 (MGA1) [MIM:250950]. MGA1 is an inborn error of leucine metabolism. It leads to an autosomal recessive syndrome with variable clinical phenotype, ranging from delayed speech development to severe psychomotor retardation, coma, failure to thrive, metabolic acidosis and dystonia. MGA1 can be distinguished from other forms of MGA by the pattern of metabolite excretion: 3- methylglutaconic acid levels are higher than those detected in other forms, whereas methylglutaric acid levels are usually only slightly elevated, and there is a high level of 3- hydroxyisovaleric acid excretion (not present in other MGA forms).
Q96GD4	Disruptive regulation of expression is a possibile mechanism of the perturbation of chromosomal integrity in cancer cells through its dominant-negative effect on cytokinesis.
Q9UQB9	Defects in AURKC are the cause of male infertility with large-headed, multiflagellar, polyploid spermatozoa [MIM:243060]; also known as infertility associated with multi-tailed spermatozoa and excessive DNA.
Q13705	Defects in ACVR2B are the cause of visceral heterotaxy autosomal type 4 (HTX4) [MIM:602730]. A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. It results in an abnormal arrangement of visceral organs, and a wide variety of congenital defects. Clinical features of visceral heterotaxy type 4 include dextrocardia, right aortic arch and a right-sided spleen, anomalies of the inferior and the superior vena cava, atrial ventricular canal defect with dextro-transposed great arteries, pulmonary stenosis, polysplenia and midline liver.
O15169	Defects in AXIN1 are involved in hepatocellular carcinoma (HCC) [MIM:114550].
O15169	Hypermethylation of the AXIN1 promoter may be associated with caudal duplication anomaly [MIM:607864]. Caudal duplication anomaly is characterized by the occurrence of duplications of different organs in the caudal region.
Q9Y2T1	Defects in AXIN2 are involved in colorectal cancer (CRC) [MIM:114500]. They appear to be specifically associated with defective mismatch repair.
Q9Y2T1	Defects in AXIN2 are the cause of oligodontia-colorectal cancer syndrome [MIM:608615]. Affected individuals manifest severe tooth agenesis and colorectal cancer or precancerous lesions of variable types.
P61769	Defects in B2M are the cause of hypercatabolic hypoproteinemia [MIM:241600]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.
P61769	Persistent high blood levels of B2M are a cause of hemodialysis-related amyloidosis (HRA) [MIM:109700]. High levels of B2M accumulate in the serum of patients with renal failure, and may lead to amyloid formation. Hemodialysis-related amyloidosis is a form of systemic amyloidosis with a predilection for the synovium and bone that occurs with a disturbingly high frequency among patients on long-term hemodialysis. The clinical features include carpal tunnel syndrome, erosive arthropathy, spondyloarthropathy, lytic bone lesions, and pathologic fractures.
P02730	Defects in SLC4A1 are the cause of elliptocytosis type 4 (EL4) [MIM:109270]. EL4 is a Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.
P02730	Defects in SLC4A1 are the cause of spherocytosis type 4 (SPH4) [MIM:612653]; also known as hereditary spherocytosis type 4 (HS4). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal.
P02730	Defects in SLC4A1 are the cause of autosomal dominant distal renal tubular acidosis (dRTA) [MIM:179800]. This disease is characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis.
P02730	Defects in SLC4A1 are the cause of autosomal recessive distal renal tubular acidosis (dRTA) [MIM:611590].
Q6Y288	Defects in B3GALTL are the cause of Peters-plus syndrome (PPS) [MIM:261540]. PPS is an autosomal recessive disorder characterized by anterior eye-chamber abnormalities, disproportionate short stature, developmental delay, characteristic craniofacial features, cleft lip and/or palate.
P15291	Defects in B4GALT1 are the cause of congenital disorder of glycosylation type 2D (CDG2D) [MIM:607091]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q9UBV7	Defects in B4GALT7 are the cause of Ehlers-Danlos syndrome progeroid type (EDSP) [MIM:130070]. EDSP is a variant form of Ehlers-Danlos syndrome characterized by progeroid facies, mild mental retardation, short stature, skin hyperextensibility, moderate skin fragility, joint hypermobility principally in digits.
Q14032	Defects in BAAT are involved in familial hypercholanemia (FHCA) [MIM:607748]. FHCA is a disorder characterized by elevated serum bile acid concentrations, itching, and fat malabsorption.
Q6ZUV0	Genetic variations in ACOT7L may be a cause of susceptibility to nasopharyngeal carcinoma type 1 (NPCA1) [MIM:607107]. A variant located in the regulatory region of the gene creates an AP1-binding site that significantly enhances binding of AP1 to the promoter, resulting in up-regulation in nasopharyngeal carcinoma.
Q8NDB2	Genetic variations in BANK1 influence susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. SLE is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system.
P51572	Microdeletions in BCAP31 are involved in the contiguous ABCD1/DXS1375E deletion syndrome (CADDS) [MIM:300475]. Patients manifest profound neonatal hypotonia, subsequent failure to thrive, and cholestatic liver disease.
P82251	Defects in SLC7A9 are a cause of non-type I cystinuria (CSNU) [MIM:220100]. CSNU arises from impaired transport of cystine and dibasic amino acids through the epithelial cells of the renal tubule and gastrointestinal tract. Three types of cystinuria have been described: type I (fully recessive or silent); type II (high excretor); type III (moderate excretor). Defects in SLC7A9 are associated with type II and type III cystinuria. They also might account for some non-classic type I cystinuria cases.
Q9UIG0	Chromosomal aberrations involving BAZ1B may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in Williams-Beuren syndrome (WBS) [MIM:194050]. WBS is a contiguous gene deletion syndrome involving genes from chromosome band 7q11.23.
Q8TAM1	Defects in BBS10 are the cause of Bardet-Biedl syndrome type 10 (BBS10) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal recessive disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation.
Q6ZW61	Defects in BBS12 are the cause of Bardet-Biedl syndrome type 12 (BBS12) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal recessive disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect. BBS12 seems to be rarely involved in oligogenic inheritance.
Q8NFJ9	Defects in BBS1 are a cause of Bardet-Biedl syndrome type 1 (BBS1) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect. Inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for disease manifestation in some cases (triallelic inheritance).
Q9BXC9	Defects in BBS2 are the cause of Bardet-Biedl syndrome type 2 (BBS2) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal recessive disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect.
Q96RK4	Defects in BBS4 are the cause of Bardet-Biedl syndrome type 4 (BBS4) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, autosomal recessive disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect.
Q8N3I7	Defects in BBS5 are a cause of Bardet-Biedl syndrome type 5 (BBS5) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect.
Q8IWZ6	Defects in BBS7 are a cause of Bardet-Biedl syndrome type 7 (BBS7) [MIM:209900]. Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by usually severe pigmentary retinopathy, early onset obesity, polydactyly, hypogenitalism, renal malformation and mental retardation. Secondary features include diabetes mellitus, hypertension and congenital heart disease. A relatively high incidence of BBS is found in the mixed Arab populations of Kuwait and in Bedouin tribes throughout the Middle East, most likely due to the high rate of consaguinity in these populations and a founder effect. Inheritance is autosomal recessive, but three mutated alleles (two at one locus, and a third at a second locus) may be required for disease manifestation in some cases (triallelic inheritance).
Q9H165	Chromosomal aberrations involving BCL11A may be a cause of lymphoid malignancies. Translocation t(2;14)(p13;q32.3) causes BCL11A deregulation and amplification.
Q63767	Appears to have a central function in transformation of some cell types.
Q9H9Y9	A chromosomal aberration involving BCAS3 may be a cause of breast cancer. Translocation t(17;20)(q23;q13) with BCAS4.
Q8TDL9	A chromosomal aberration involving BCAS4 may be a cause of breast cancer. Translocation t(17;20)(q23;q13) with BCAS3.
Q9HAY6	Defects in BCMO1 are the cause of autosomal dominant hypercarotenemia and vitamin A deficiency [MIM:115300]. Vitamin A is essential for normal embryonic development as well as normal physiological functions in children and adults. Hypercarotenemia is characterized by an excess carotene in the serum, but unlike excess vitamin A, carotene is non-toxic. So far, only a few cases of excess vitamin A have been reported. Individuals were thought to be vitamin A deficient due to an impairment in the conversion of carotenoids to retinal in the intestine.
O95999	A chromosomal aberration involving BCL10 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(1;14)(p22;q32). Although the BCL10/IgH translocation leaves the coding region of BCL10 intact, frequent BCL10 mutations could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
O95999	Defects in BCL10 are involved in various types of cancer.
P10415	A chromosomal aberration involving BCL2 may be a cause of follicular lymphoma (FL) [MIM:151430]; also known as type II chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
P20749	A chromosomal aberration involving BCL3 may be a cause of B-cell chronic lymphocytic leukemia (B-CLL). Translocation t(14;19)(q32;q13.1) with immunoglobulin gene regions.
P41182	Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions.
P41182	A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1.
P41182	A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
Q4VC05	Chromosomal aberrations involving BCL7A may be a cause of B-cell non-Hodgkin lymphoma. Three-way translocation t(8;14;12)(q24.1;q32.3;q24.1) with MYC and with immunoglobulin gene regions.
Q9BQE9	Haploinsufficiency of BCL7B may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in Williams-Beuren syndrome (WBS) [MIM:194050]. WBS is a rare developmental disorder. It is a contiguous gene deletion syndrome involving genes from chromosome band 7q11.23.
P0C6P0	A chromosomal aberration involving BCL8 has been observed in diffuse large cell lymphoma (DLCL). Translocation t(14;15)(q32;q11-q13). The BCL8/IgH translocation leaves the coding region of BCL8 intact, but may have pathogenic effects due to alterations in the expression level of BCL8.
O00512	A chromosomal aberration involving BCL9 is found in a patient with precusor B-cell acute lymphoblastic leukemia (ALL). Translocation t(1;14)(q21;q32). This translocation leaves the coding region intact, but may have pathogenic effects due to alterations in the expression level of BCL9. Several cases of translocations within the 3'-UTR of BCL9 have been found in B-cell malignancies.
Q9HCJ7	Defects in BCOR are the cause of microphthalmia syndromic type 2 (MCOPS2) [MIM:300166]. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS2 is a very rare multiple congenital anomaly syndrome characterized by eye anomalies (congenital cataract, microphthalmia, or secondary glaucoma), facial abnormalities (long narrow face, high nasal bridge, pointed nose with cartilages separated at the tip, cleft palate, or submucous cleft palate), cardiac anomalies (atrial septal defect, ventricular septal defect, or floppy mitral valve) and dental abnormalities (canine radiculomegaly, delayed dentition, oligodontia, persistent primary teeth, or variable root length).
P11274	A chromosomal aberration involving BCR is a cause of chronic myeloid leukemia (CML) [MIM:608232]. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
Q9Y276	Defects in BCS1L are the cause of GRACILE syndrome [MIM:603358]. GRACILE stands for 'growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death'. It is a recessively inherited lethal disease characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism.
Q9Y276	Defects in BCS1L are a cause of mitochondrial complex III deficiency (CIII deficiency) [MIM:124000]. CIII deficiency is characterized by congenital lactic acidosis. Patients had severe failure to thrive, liver dysfunction and renal tubulopathy.
Q9Y276	Defects in BCS1L are the cause of Bjoernstad syndrome (BJS) [MIM:262000]. BJS is an autosomal recessive condition characterized by sensorineural hearing loss and pili torti. The hearing loss in BJS is congenital and of variable severity. Pili torti (twisted hairs), a condition in which the hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair extremely brittle, is usually recognized early in childhood.
Q9UC24	Defects in BDNF are a cause of congenital central hypoventilation syndrome (CCHS) [MIM:209880]; also known as congenital failure of autonomic control or Ondine curse. CCHS is a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. CCHS is frequently complicated with neurocristopathies such as Hirschsprung disease that occurs in about 16% of CCHS cases.
Q9UC24	Haploinsufficiency of BDNF is strongly associated with Wilms tumor, aniridia, genitourinary anomalies, mental retardation, and obesity syndrome (WAGRO) [MIM:612469]. In a subgroup of individuals with the WAGR syndrome, obesity develops. The phenotype in this subset is associated with haploinsufficiency for the BDNF gene.
O76090	Defects in BEST1 are the cause of vitelliform macular dystrophy type 2 (VMD2) [MIM:153700]; also known as Best macular dystrophy (BMD). VMD2 is an autosomal dominant form of macular degeneration that usually begins in childhood or adolescence. VMD2 is characterized by typical 'egg-yolk' macular lesions due to abnormal accumulation of lipofuscin within and beneath the retinal pigment epithelium cells. Progression of the disease leads to destruction of the retinal pigment epithelium and vision loss.
O76090	Defects in BEST1 may be a cause of concentric annular macular dystrophy (MCDCA) [MIM:153870]; also known as bull's eye maculopathy.
O76090	Defects in BEST1 are a cause of adult-onset vitelliform macular dystrophy (AVMD) [MIM:608161]. AVMD is a rare autosomal dominant disorder with incomplete penetrance and highly variable expression. Patients usually become symptomatic in the fourth or fifth decade of life with a protracted disease of decreased visual acuity.
O76090	Defects in BEST1 are the cause of bestrophinopathy autosomal recessive (ARB) [MIM:611809]. A retinopathy characterized by central visual loss, an absent electro-oculogram light rise, and a reduced electroretinogram.
O76090	Defects in BEST1 are the cause of vitreoretinochoroidopathy autosomal dominant (ADVIRC) [MIM:193220]. A disorder characterized by vitreoretinochoroidal dystrophy. The clinical presentation is variable and may be associated with cataract, nanophthalmos, microcornea, shallow anterior chamber, and glaucoma.
Q12934	Defects in BFSP1 are the cause of cataract cortical juvenile-onset (CCJO) [MIM:611391]. A juvenile-onset cataract with opacities restricted to the cortex of the lens, not involving the nucleus.
Q13515	Defects in BFSP2 are the cause of cataract autosomal dominant BFSP2-related (ADC-BFSP2) [MIM:611597]; also known as cataract autosomal dominant multiple types 1. Cataract is an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. Cataract autosomal dominant BFSP2-related is characterized by a variable phenotype that may or may not be consistent within a family. The opacities can be nuclear, sutural, stellate cortical, lamellar, cortical, nuclear embryonic, Y-sutural, punctate cortical, congenital or with juvenile- and adult-onset.
P16278	Defects in GLB1 are the cause of GM1-gangliosidosis type 1 (GM1G1) [MIM:230500]; also known as infantile GM1- gangliosidosis. GM1-gangliosidosis is an autosomal recessive lysosomal storage disease marked by the accumulation of GM1 gangliosides, glycoproteins and keratan sulfate primarily in neurons of the central nervous system. GM1G1 is characterized by onset within the first three months of life, central nervous system degeneration, coarse facial features, hepatosplenomegaly, skeletal dysmorphology reminiscent of Hurler syndrome, and rapidly progressive psychomotor deterioration. Urinary oligosaccharide levels are high. It leads to death usually between the first and second year of life.
P16278	Defects in GLB1 are the cause of GM1-gangliosidosis type 2 (GM1G2) [MIM:230600]; also known as late infantile/juvenile GM1- gangliosidosis. GM1G2 is characterized by onset between ages 1 and 5. The main symptom is locomotor ataxia, ultimately leading to a state of decerebration with epileptic seizures. Patients do not display the skeletal changes associated with the infantile form, but they nonetheless excrete elevated amounts of beta-linked galactose-terminal oligosaccharides. Inheritance is autosomal recessive.
P16278	Defects in GLB1 are the cause of GM1-gangliosidosis type 3 (GM1G3) [MIM:230650]; also known as adult or chronic GM1- gangliosidosis. GM1G3 is characterized by a variable phenotype. Patients show mild skeletal abnormalities, dysarthria, gait disturbance, dystonia and visual impairment. Visceromegaly is absent. Intellectual deficit can initially be mild or absent but progresses over time. Inheritance is autosomal recessive.
P16278	Defects in GLB1 are the cause of mucopolysaccharidosis type 4B (MPS4B) [MIM:253010]; also known as Morquio syndrome B. MPS4B is a form of mucopolysaccharidosis type 4, an autosomal recessive lysosomal storage disease characterized by intracellular accumulation of keratan sulfate and chondroitin-6-sulfate. Key clinical features include short stature, skeletal dysplasia, dental anomalies, and corneal clouding. Intelligence is normal and there is no direct central nervous system involvement, although the skeletal changes may result in neurologic complications. There is variable severity, but patients with the severe phenotype usually do not survive past the second or third decade of life.
Q53XM1	Defects in TGFBI are the cause of epithelial basement membrane corneal dystrophy (EBMD) [MIM:121820]; also known as Cogan corneal dystrophy or map-dot-fingerprint type corneal dystrophy. EBMD is a bilateral anterior corneal dystrophy characterized by grayish epithelial fingerprint lines, geographic map-like lines, and dots (or microcysts) on slit-lamp examination. Pathologic studies show abnormal, redundant basement membrane and intraepithelial lacunae filled with cellular debris. Although this disorder usually is not considered to be inherited, families with autosomal dominant inheritance have been identified.
Q53XM1	Defects in TGFBI are the cause of corneal dystrophy Groenouw type 1 (CDGG1) [MIM:121900]; also known as corneal dystrophy granular type. Inheritance is autosomal dominant. Corneal dystrophies show progressive opacification of the cornea leading to severe visual handicap.
Q53XM1	Defects in TGFBI are the cause of corneal dystrophy lattice type 1 (CDL1) [MIM:122200]. Inheritance is autosomal dominant.
Q53XM1	Defects in TGFBI are a cause of corneal dystrophy Thiel- Behnke type (CDTB) [MIM:602082]; also known as corneal dystrophy of Bowman layer type 2 (CDB2).
Q53XM1	Defects in TGFBI are the cause of Reis-Buecklers corneal dystrophy (CDRB) [MIM:608470]; also known as corneal dystrophy of Bowman layer type 1 (CDB1).
Q53XM1	Defects in TGFBI are the cause of lattice corneal dystrophy type 3A (CDL3A) [MIM:608471]. CDL3A clinically resembles to lattice corneal dystrophy type 3, but differs in that its age of onset is 70 to 90 years. It has an autosomal dominant inheritance pattern.
Q53XM1	Defects in TGFBI are the cause of Avellino corneal dystrophy (ACD) [MIM:607541]. ACD could be considered a variant of granular dystrophy with a significant amyloidogenic tendency. Inheritance is autosomal dominant.
O18835	Defects in GUSB are the cause of mucopolysaccharidosis type VII (MPS VII), an inherited disease reported in humans, mice, cats, and dogs.
O97524	Defects in GUSB are the cause of mucopolysaccharidosis type VII (MPS VII), an inherited disease reported in humans, mice, cats, and dogs.
P08236	Defects in GUSB are the cause of mucopolysaccharidosis type 7 (MPS7) [MIM:253220]; also known as Sly syndrome. MPS7 is an autosomal recessive lysosomal storage disease characterized by inability to degrade glucuronic acid-containing glycosaminoglycans. The phenotype is highly variable, ranging from severe lethal hydrops fetalis to mild forms with survival into adulthood. Most patients with the intermediate phenotype show hepatomegaly, skeletal anomalies, coarse facies, and variable degrees of mental impairment.
P08236	Mucopolysaccharidosis type 7 is associated with non- immune hydrops fetalis [MIM:236750]. Hydrops fetalis is a generalized edema of the fetus with fluid accumulation in the body cavities.
Q9Y6D5	Defects in ARFGEF2 are the cause of autosomal recessive periventricular nodular heterotopia type 2 (PVNH2) [MIM:608097]; also known as periventricular heterotopia with microcephaly autosomal recessive. PVNH is a developmental disorder characterized by the presence of periventricular nodules of cerebral gray matter, resulting from a failure of neurons to migrate normally from the lateral ventricular proliferative zone, where they are formed, to the cerebral cortex. PVNH2 is an autosomal recessive form characterized by microcephaly (small brain), severe developmental delay and recurrent infections. No anomalies extrinsic to the central nervous system, such as dysmorphic features or grossly abnormal endocrine or other conditions, are associated with PVNH2.
O75514	Defects in BIN1 are the cause of centronuclear myopathy autosomal recessive (ARCNM) [MIM:255200]; also known as autosomal recessive myotubular myopathy. Centronuclear myopathies are congenital muscle disorders characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.
Q13489	A chromosomal aberration involving BIRC3 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with MALT1. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.
Q6QNY0	Defects in BLOC1S3 are the cause of Hermansky-Pudlak syndrome type 8 (HPS8) [MIM:203300]. Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous, rare, autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS.
Q5U5M8	Defects in Bloc1s3 are the cause of the reduced pigmentation (rp) mutation phenotype, a mouse model for human Hermansky-Pudlak syndrome (HPS). Rp mice are characterized by abnormal melanosomes and display altered expression levels of the proteins of the BLOC1 complex.
P54132	Defects in BLM are the cause of Bloom syndrome (BLM) [MIM:210900]. BLM is an autosomal recessive disorder characterized by proportionate pre- and postnatal growth deficiency, sun- sensitive telangiectatic hypo- and hyperpigmented skin, predisposition to malignancy, and chromosomal instability.
Q8WV28	Defects in BLNK are the cause of hypoglobulinemia and absent B-cells [MIM:604515]. This is a developmental blockage at the pro- to pre-B-cell transition.
Q8WV28	In 6 of 34 childhood pre-B acute lymphoblastic leukemia (ALL) samples that were tested showed a complete loss or drastic reduction of BLNK expression.
O95972	Defects in BMP15 are the cause of ovarian dysgenesis type 2 (ODG2) [MIM:300510]; also known as X-linked hypergonadotropic ovarian dysgenesis or hypergonadotropic ovarian failure due to ovarian dysgenesis. Ovarian dysgenesis leads to ovarian failure and accounts for about half of the cases of primary amenorrhea.
O95972	Defects in BMP15 are the cause of premature ovarian failure type 4 (POF4) [MIM:300510]. POF4 is a disorder with cessation of ovarian function before the age of 40 years and elevated gonadotrophins. It may result from a decreased pool of primordial follicles, an accelerated rate of follicular atresia or dysfunction in follicular recruitment or maturation. A decreased pool of primordial follicles can be caused by ovarian dysgenesis in some.
P12644	Defects in BMP4 are the cause of microphthalmia syndromic type 6 (MCOPS6) [MIM:607932]; also known as microphthalmia and pituitary anomalies or microphthalmia with brain and digit developmental anomalies. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS6 is characterized by microphthalmia/anophthalmia associated with facial, genital, skeletal, neurologic and endocrine anomalies.
P12644	Defects in BMP4 are the cause of non-syndromic orofacial cleft type 11 (OFC11) [MIM:600625]. Non-syndromic orofacial cleft is a common birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two- third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum. OFC11 is an unusual anomaly consisting of a paramedian scar of the upper lip with an appearance suggesting that a typical cleft lip was corrected in utero.
Q13873	Defects in BMPR2 are the cause of primary pulmonary hypertension (PPH1) [MIM:178600]. PPH1 is a rare autosomal dominant disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial PPH1 is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.
Q13873	Defects in BMPR2 are a cause of pulmonary venoocclusive disease (PVOD) [MIM:265450]. PVOD is a rare form of pulmonary hypertension in which the vascular changes originate in the small pulmonary veins and venules. The pathogenesis is unknown and any link with PPH1 has been speculative. The finding of PVOD associated with a BMPR2 mutation reveals a possible pathogenetic connection with PPH1.
P36894	Defects in BMPR1A are a cause of juvenile polyposis syndrome (JPS) [MIM:174900]; also known as juvenile intestinal polyposis (JIP). JPS is an autosomal dominant gastrointestinal hamartomatous polyposis syndrome in which patients are at risk for developing gastrointestinal cancers. The lesions are typified by a smooth histological appearance, predominant stroma, cystic spaces and lack of a smooth muscle core. Multiple juvenile polyps usually occur in a number of Mendelian disorders. Sometimes, these polyps occur without associated features as in JPS; here, polyps tend to occur in the large bowel and are associated with an increased risk of colon and other gastrointestinal cancers.
P36894	Defects in BMPR1A are a cause of Cowden disease (CD) [MIM:158350]. CD is an autosomal dominant cancer syndrome characterized by multiple hamartomas and by a high risk for breast, thyroid and endometrial cancers.
P36894	Defects in BMPR1A are the cause of hereditary mixed polyposis syndrome 2 (HMPS2) [MIM:610069]. Hereditary mixed polyposis syndrome (HMPS) is characterized by atypical juvenile polyps, colonic adenomas, and colorectal carcinomas.
P36894	A microdeletion of chromosome 10q23 involving BMPR1A and PTEN is a cause of chromosome 10q23 deletion syndrome [MIM:612242]. This syndrome shows overlapping features of the following three disorders: Bannayan-Zonana syndrome, Cowden disease and juvenile polyposis syndrome. The 10q23 microdeletion is also found in patients manifesting juvenile polyposis of infancy without cognitive disability. Juvenile polyposis of infancy is characterized by the appearance of extensive gastrointestinal juvenile hamartomatous polyposis in the first months of life.
O00238	Defects in BMPR1B are the cause of acromesomelic chondrodysplasia with genital anomalies (AMDGA) [MIM:609441]. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs, and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob- like fingers).
O00238	Defects in BMPR1B are a cause of brachydactyly type A2 (BDA2) [MIM:112600]. Brachydactylies (BDs) are a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. They have been classified on an anatomic and genetic basis into five groups, A to E, including three subgroups (A1 to A3) that usually manifest as autosomal dominant traits. BDA2 was described first in a large Norwegian kindred. BDA2 is caused by mutations in BMPR1B gene and studies demonstrate that these mutations function as dominant negatives in vitro and in vivo.
P50747	Defects in HLCS are the cause of holocarboxylase synthetase deficiency (HLCS deficiency) [MIM:253270]; also known as biotin-responsive multiple carboxylase deficiency. HLCS deficiency is a neonatal form of multiple carboxylase deficiency, an autosomal recessive disorder characterized by metabolic ketoacidosis, hyperammonemia, excretion of abnormal organic acid metabolites and dermatitis. Clinical and biochemical symptoms improve dramatically with administration of biotin.
O15178	Genetic variations in T are associated with susceptibility to neural tube defects (NTD) [MIM:182940]. NTD are common congenital malformations. Spina bifida, which results from malformations in the caudal region of the neural tube, is compatible with life but associated with significant morbidity, including lower limb paralysis.
P20293	Embryo lacking the T gene fail to form the notochord, the entire posterior region and the allantois, and die at about 10 days of gestation.
P15056	Defects in BRAF are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio- cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant.
P15056	Defects in BRAF are involved in a wide range of cancers.
P15056	Defects in BRAF are involved in lung cancer [MIM:211980].
P15056	Defects in BRAF are involved in non-Hodgkin lymphoma (NHL) [MIM:605027]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss.
P15056	Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:114500].
P15056	Defects in BRAF are found in Noonan syndrome, an autosomal dominant dysmorphic syndrome characterized by hypertelorism, a downward eyeslant, and low-set posteriorly rotated ears. Other features include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, epicanthic folds, deafness, motor delay, and a bleeding diathesis.
P15056	Defects in BRAF are found in some cases of LEOPARD syndrome. LEOPARD syndrome is characterized by multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness.
P28028	Participates in a chromosomal translocation that produces a Tif1a-BRAF (T18) oncogene originally isolated from a furfural- induced hepatoma.
P38398	Defects in BRCA1 are a cause of genetic susceptibility to breast cancer (BC) [MIM:113705, 114480]. BC is an extremely common malignancy, affecting one in eight women during their lifetime. A positive family history has been identified as major contributor to risk of development of the disease, and this link is striking for early-onset breast cancer. Mutations in BRCA1 are thought to be responsible for 45% of inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold increased risk of colon cancer, whereas male carriers face a 3-fold increased risk of prostate cancer. Cells lacking BRCA1 show defects in DNA repair by homologous recombination.
P38398	Defects in BRCA1 are a cause of susceptibility to familial breast-ovarian cancer type 1 (BROVCA1) [MIM:604370]. Mutations in BRCA1 are thought to be responsible for more than 80% of inherited breast-ovarian cancer.
P38398	Defects in BRCA1 are a cause of genetic susceptibility to ovarian cancer [MIM:113705].
P51587	Defects in BRCA2 are a cause of genetic susceptibility to breast cancer (BC) [MIM:612555, 114480]; also called susceptibility to familial breast-ovarian cancer type 2 (BROVCA2). BC is an extremely common malignancy, affecting one in eight women during their lifetime. A positive family history has been identified as major contributor to risk of development of the disease, and this link is striking for early-onset breast cancer. Mutations in BRCA2 are thought to be responsible for some inherited breast cancer. It is linked with male breast cancer.
P51587	Defects in BRCA2 are the cause of Fanconi anemia complementation group D type 1 (FANCD1) [MIM:605724]. Fanconi anemia (FA) [MIM:227650] is an autosomal recessive disorder affecting all bone marrow elements and associated with cardiac, renal and limb malformations as well as dermal pigmentary changes.
B4DQN7	A chromosomal aberration involving BRCC3 is a cause of pro-lymphocytic T-cell leukemia (T-PLL). Translocation t(X;14)(q28;q11) with TCRA.
Q15059	A chromosomal aberration involving BRD3 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;9)(q14;q34) with NUT which produces a BRD3-NUT fusion protein.
O60885	A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.
Q9BZH6	A chromosomal aberration involving BRWD2 is found in a form of glioblastoma. Translocation t(10;19)(q26;q13.3) with ZNF320.
Q6RI45	A chromosomal aberration involving BRWD3 can be found in patients with B-cell chronic lymphocytic leukemia (B-CLL). Translocation t(X;11)(q21;q23) with ARHGAP20 does not result in fusion transcripts but disrupts both genes.
Q6RI45	Defects in BRWD3 are the cause of mental retardation X- linked type 93 (MRX93) [MIM:300659]; also known as mental retardation X-linked with macrocephaly. Mental retardation is characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Mentally retarded individuals are at least twice as likely to have macrocephaly than are their intellectually normal peers.
Q96G97	Defects in BSCL2 are the cause of congenital generalized lipodystrophy type 2 (CGL2) [MIM:269700]. Congenital generalized lipodystrophy is an autosomal recessive disorder characterized by a near absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes.
Q96G97	Defects in BSCL2 are the cause of spastic paraplegia type 17 (SPG17) [MIM:270685]; also known as Silver spastic paraplegia syndrome. Spastic paraplegia is a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. SPG17 is characterized by prominent amyotrophy of the hand muscles, the presence of mild to severe pyramidal tract signs, and spastic paraplegia. SPG17 is a motor neuron disease overlapping with distal spinal muscular atrophy type 5.
Q96G97	Defects in BSCL2 are a cause of distal hereditary motor neuropathy type 5 (HMN5) [MIM:600794]; also known aS distal hereditary motor neuropathy type V (DSMAV). HMN5 is an autosomal dominant disorder characterized by degeneration of motor nerve fibers, predominantly in limb distal regions.
Q8WZ55	Defects in BSND are the cause of Bartter syndrome type 4 (BS4) [MIM:602522]; also known as infantile Bartter syndrome with sensorineural deafness. BS refers to a group of autosomal recessive disorders characterized by impaired salt reabsorption in the thick ascending loop of Henle with pronounced salt wasting, hypokalemic metabolic alkalosis, and varying degrees of hypercalciuria. BS4 is associated with sensorineural deafness.
Q96Q07	Genetic variations in BTBD9 are associated with susceptibility to restless legs syndrome type 6 (RLS6) [MIM:611185]; also called periodic limb movements in sleep. Restless legs syndrome (RLS) is a neurologic disorder characterized by an uncontrollable urge to move the legs during periods of rest. The majority of patients with RLS also have periodic limb movements in sleep, which are characterized by involuntary, highly stereotypical, regularly occurring limb movements that occur during sleep.
P43251	Defects in BTD are the cause of biotinidase deficiency (BTD deficiency) [MIM:253260]; also called late-onset multiple carboxylase deficiency. BTD deficiency is a juvenile form of multiple carboxylase deficiency, an autosomal recessive disorder of biotin metabolism, characterized by ketoacidosis, hyperammonemia, excretion of abnormal organic acid metabolites, and dermatitis. BTD deficiency is characterized by seizures, hypotonia, skin rash, alopecia, ataxia, hearing loss, and optic atrophy. If untreated, symptoms usually become progressively worse, and coma and death may occur.
P62324	A chromosomal aberration involving BTG1 may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with MYC.
Q06187	Defects in BTK are the cause of X-linked agammaglobulinemia (XLA) [MIM:300755]; also known as X-linked agammaglobulinemia type 1 (AGMX1) or immunodeficiency type 1 (IMD1). XLA is a humoral immunodeficiency disease which results in developmental defects in the maturation pathway of B-cells. Affected boys have normal levels of pre-B-cells in their bone marrow but virtually no circulating mature B-lymphocytes. This results in a lack of immunoglobulins of all classes and leads to recurrent bacterial infections like otitis, conjunctivitis, dermatitis, sinusitis in the first few years of life, or even some patients present overwhelming sepsis or meningitis, resulting in death in a few hours. Treatment in most cases is by infusion of intravenous immunoglobulin.
Q06187	Defects in BTK may be the cause of X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA- IGHD) [MIM:307200]; also known as agammaglobulinemia and isolated growth hormone deficiency or Fleisher syndrome or isolated growth hormone deficiency type 3 (IGHD3). In rare cases XLA is inherited together with isolated growth hormone deficiency (IGHD).
P35991	Defects in Btk are the cause of murine X-linked immunodeficiency (XID).
Q5SU36	Individuals expressing isoform 3 have a genetic predisposition to develop susceptibility to sarcoidosis type 2 (SS2) [MIM:612387]. Sarcoidosis is a disease of unknown etiology in which there are chronic inflammatory granulomatous lesions in lymph nodes and other organs.
Q59HH6	Defects in BUB1B are associated with tumor formation.
Q59HH6	Defects in BUB1B are the cause of premature chromatid separation trait (PCS) [MIM:176430]. PCS consists of separate and splayed chromatids with discernible centromeres and involves all or most chromosomes of a metaphase. It is found in up to 2% of metaphases in cultured lymphocytes from approximately 40% of normal individuals. When PCS is present in 5% or more of cells, it is known as the heterozygous PCS trait and has no obvious phenotypic effect, although some have reported decreased fertility. Inheritance is autosomal dominant.
Q59HH6	Defects in BUB1B are the cause of mosaic variegated aneuploidy syndrome (MVA) [MIM:257300]. MVA is a severe autosomal recessive developmental disorder characterized by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. The proportion of aneuploid cells varies but is usually more than 25% and is substantially greater than in normal individuals. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay, and a broad spectrum of additional congenital abnormalities and medical conditions may also occur. The risk of malignancy is high, with rhabdomyosarcoma, Wilms tumor and leukemia reported in several cases. MVA is caused by biallelic mutations in the BUB1B gene.
Q9Z1S0	Defects in Bub1b are involved in the development of lung and intestinal adenocarcinomas after exposure to a carcinogen.
Q9UBR1	Defects in UPB1 are the cause of beta-ureidopropionase deficiency [MIM:606673]. It is characterized by muscular hypotonia, dystonic movements, scoliosis, microcephaly and severe developmental delay. Patients show strongly elevated levels of N- carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in plasma, cerebrospinal fluid and urine.
P15538	Defects in CYP11B1 are the cause of adrenal hyperplasia type 4 (AH4) [MIM:202010]. AH4 is a form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: "salt wasting" (SW, the most severe type), "simple virilizing" (SV, less severely affected patients), with normal aldosterone biosynthesis, "non-classic form" or late onset (NC or LOAH), and "cryptic" (asymptomatic). AH4 patients usually have hypertension.
P15538	An anti-Lepore-type fusion of the CYP11B1 and CYP11B2 genes is a cause of glucocorticoid-remediable aldosteronism (GRA) [MIM:103900].
P19099	Defects in CYP11B2 are the cause of corticosterone methyloxidase type 1 deficiency (CMO-1 deficiency) [MIM:203400]; also known as aldosterone deficiency due to defect in 18- hydroxylase or aldosterone deficiency I. CMO-1 deficiency is an autosomal recessive disorder of aldosterone biosynthesis. There are two biochemically different forms of selective aldosterone deficiency be termed corticosterone methyloxidase (CMO) deficiency type 1 and type 2. In CMO-1 deficiency, aldosterone is undetectable in plasma, while its immediate precursor, 18- hydroxycorticosterone, is low or normal.
P19099	Defects in CYP11B2 are the cause of corticosterone methyloxidase type 2 deficiency (CMO-2 deficiency) [MIM:610600]. CMO-2 is an autosomal recessive disorder of aldosterone biosynthesis. In CMO-2 deficiency, aldosterone can be low or normal, but at the expense of increased secretion of 18- hydroxycorticosterone. Consequently, patients have a greatly increased ratio of 18-hydroxycorticosterone to aldosterone and a low ratio of corticosterone to 18-hydroxycorticosterone in serum.
P19099	An anti-Lepore-type fusion of the CYP11B2 and CYP11B1 genes is a cause of glucocorticoid-remediable aldosteronism (GRA) [MIM:103900].
Q96EU7	Defects in C1GALT1C1 are the cause of Tn syndrome [MIM:300622]. Tn syndrome is a rare autoimmune disease caused by somatic mutation in the C1GALT1C1 gene in which subpopulations of blood cells of all lineages carry an incompletely glycosylated membrane glycoprotein, i.e., the Tn antigen. Since leukocytes and platelets are affected as well as red cells, anemia, leukopenia and thrombocytopenia are features. Tn-polyagglutinability is sometimes associated with leukemia or is a preleukemic state.
P02745	Defects in C1QA are a cause of C1q deficiency [MIM:120550]. It is a rare genetic disorder which is associated with recurrent infections and a high prevalence of lupus erythematosus-like symptoms. It is characterized by a loss of activation of the complement classical pathway.
P02746	Defects in C1QB are a cause of C1q deficiency [MIM:120570]. It is a rare genetic disorder which is associated with recurrent infections and a high prevalence of lupus erythematosus-like symptoms. It is characterized by a loss of activation of the complement classical pathway.
P02747	Defects in C1QC are a cause of C1q deficiency [MIM:120575]. It is a rare genetic disorder which is associated with recurrent infections and a high prevalence of lupus erythematosus-like symptoms. It is characterized by a loss of activation of the complement classical pathway.
Q9BXJ0	Defects in C1QTNF5 are a cause of late-onset retinal degeneration (LORD) [MIM:605670]. LORD is an autosomal dominant disorder characterized by onset in the fifth to sixth decade with night blindness and punctate yellow-white deposits in the retinal fundus, progressing to severe central and peripheral degeneration, with choroidal neovascularization and chorioretinal atrophy.
Q9UCV4	Defects in C1S are the cause of selective C1s deficiency [MIM:120580]; that is associated with early onset multiple autoimmune diseases.
P11586	Defects in MTHFD1 may be a cause of susceptibility to folate-sensitive neural tube defects (folate-sensitive NTD) [MIM:601634]. The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. Genetic defects in MTHFD1 may affect the risk of spina bifida via the maternal rather than the embryonic genotype.
P11586	Genetic variation in MTHFD1 could be associated with susceptibility to colorectal cancer (CRC) [MIM:114500].
Q6P1N0	Defects in CC2D1A are the cause of mental retardation autosomal recessive type 3 (MRT3) [MIM:608443]. Patients display severe mental retardation and psychomotor development delay in early childhood. Non-syndromic mental retardation patients do not manifest other clinical signs.
Q9P2K1	Defects in CC2D2A are the cause of Meckel syndrome type 6 (MKS6) [MIM:612284]. MKS is an autosomal recessive disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly.
Q9P2K1	Defects in CC2D2A are the cause of Joubert syndrome type 9 (JBTS9) [MIM:612285]. JBTS is an autosomal recessive disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease.
P33076	Defects in CIITA are a cause of bare lymphocyte syndrome type 2 (BLS2) [MIM:209920]; also known as hereditary MHC class II deficiency or HLA class II-deficient combined immunodeficiency. BLS2 is a severe combined immunodeficiency disease with early onset. It is characterized by a profound defect in constitutive and interferon-gamma induced MHC II expression, absence of cellular and humoral T-cell response to antigen challenge, hypogammaglobulinemia and impaired antibody production. The consequence include extreme susceptibility to viral, bacterial and fungal infections.
Q99643	Defects in SDHC are the cause of autosomal dominant non- chromaffin paragangliomas type 3 (PGL3) [MIM:605373]. Non- chromaffin paragangliomas are usually benign, neural crest derived tumors of parasympathetic ganglia.
Q99643	Defects in SDHC are a cause of paraganglioma and gastric stromal sarcoma [MIM:606864]; also known as Carney-Stratakis syndrome. Gastrointestinal stromal tumors may be sporadic or inherited in an autosomal dominant manner, alone or as a component of a syndrome associated with other tumors, such as in the context of neurofibromatosis type 1 (NF1). Patients have both gastrointestinal stromal tumors and paragangliomas. Susceptibility to the tumors was inherited in an apparently autosomal dominant manner, with incomplete penetrance.
Q920H6	Defects in Cacna2d2 are the cause of ducky phenotype (du). Du mice have spike-wave seizures characteristic of absence epilepsy and ataxia, with accompanying decreased calcium channel current in cerebellar Purkinje cells.
Q7Z3S7	Defects in CACNA2D4 are the cause of retinal cone dystrophy 4 (RCD4) [MIM:610478]. RCD4 is characterized by minimal symptoms except for slowly progressive reduction in visual acuity.
Q5RJF7	Defects in Cacna2d4 are a cause of cone-rod dysfunction. Mice display affected retinal ribbon-type synapses. The retinopathy is accompanied by a substantial loss in the activities of the second-order neurons. Rod photoreceptor responses are maintained with reduced amplitude, whereas cone activities are absent.
P57796	Defects in CABP4 are the cause of congenital stationary night blindness type 2B (CSNB2B) [MIM:610427]. Congenital stationary night blindness is a non-progressive retinal disorder characterized by impaired night vision.
Q99793	Defects in CACNA1A are the cause of spinocerebellar ataxia type 6 (SCA6) [MIM:183086]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA6 is mainly caused by expansion of a CAG repeat in the coding region of CACNA1A. There seems to be a correlation between the repeat number and earlier onset of the disorder.
Q99793	Defects in CACNA1A are the cause of familial hemiplegic migraine (FHM) [MIM:141500]; also known as migraine familial hemiplegic 1 (MHP1). FHM, a rare autosomal dominant subtype of migraine with aura, is associated with ictal hemiparesis and, in some families, progressive cerebellar atrophy.
Q99793	Defects in CACNA1A are the cause of episodic ataxia type 2 (EA2) [MIM:108500]; also known as acetazolamide-responsive hereditary paroxysmal cerebellar ataxia (APCA). EA2 is an autosomal dominant disorder characterized by acetozolamide- responsive attacks of ataxia, migraine-like symptoms, interictal nystagmus, and cerebellar atrophy.
P97445	Defects in Cacna1a are the cause of a delayed-onset, recessive neurological disorder seen in tottering (tg) mutants, resulting in ataxia, motor seizures and behavioral absence seizures resembling petit mal epilepsy (or absence epilepsy) in humans. There are two more alleles: leaner (tg(lA)), that is characterized by severe ataxia and frequent death past weaning, but no motor seizures; and rolling Nagoya (tg(rol)), that presents an intermediary phenotype, the ataxia being somewhat more severe that with tg, but without motors seizures. Selective degeneration of cerebellar Purkinje cells has been shown for all these types of mutants.
Q6PKM7	Defects in CACNA1C are the cause of Timothy syndrome (TS) [MIM:601005]. TS is a disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities and autism.
Q6PKM7	Defects in CACNA1C are the cause of Brugada syndrome type 3 (BRS3) [MIM:611875]. BRS3 is a heart disease characterized by the association of Brugada syndrome with shortened QT intervals. Brugada syndrome is a tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset.
O60840	Defects in CACNA1F are the cause of congenital stationary night blindness type 2A (CSNB2A) [MIM:300071]. Congenital stationary night blindness is a non-progressive retinal disorder characterized by impaired night vision.
O60840	Defects in CACNA1F are the cause of cone-rod dystrophy X- linked type 3 (CORDX3) [MIM:300476]. CORDs are inherited retinal dystrophies belonging to the group of pigmentary retinopathies. CORDs are characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa.
O60840	Defects in CACNA1F are the cause of Aaland island eye disease (AIED) [MIM:300600]; also known as Forsius-Eriksson type ocular albinism. On the Aaland island in the Baltic Sea, AIED is an X-linked recessive retinal disease characterized by a combination of fundus hypopigmentation, decreased visual acuity due to foveal hypoplasia, nystagmus, astigmatism, protan color vision defect, myopia, and defective dark adaptation. Except for progression of axial myopia, the disease can be considered to be a stationary condition. Electroretinography reveals abnormalities in both photopic and scotopic functions.
O95180	Defects in CACNA1H are a cause of susceptibility to idiopathic generalized epilepsy type 6 (IGE6) [MIM:611942]. IGE is characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. IGE6 is a polygenic and multifactorial disease.
Q13698	Defects in CACNA1S are a cause of periodic paralysis hypokalemic (HOKPP) [MIM:170400]; also designated HYPOPP. HOKPP is an autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels.
Q13698	Defects in CACNA1S are the cause of malignant hyperthermia susceptibility type 5 (MHS5) [MIM:601887]; an autosomal dominant disorder that is potentially lethal in susceptible individuals on exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants.
Q02789	Defects in Cacna1s are the cause of muscular dysgenesis (MDG), a lethal autosomal recessive disorder in which there is total lack of excitation-contraction coupling in homozygotes, and which results in complete skeletal muscle paralysis. A single nucleotide deletion yields a protein with an altered and truncated C-terminus.
Q96NZ3	Defects in CACNB2 are the cause of Brugada syndrome type 4 (BRS4) [MIM:611876]. BRS4 is a heart disease characterized by the association of Brugada syndrome with shortened QT intervals. Brugada syndrome is a tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs (called ventricular fibrillation), the individual will faint and may die in a few minutes if the heart is not reset.
O00305	Genetic variations in CACNB4 are the cause of susceptibility to idiopathic generalized epilepsy type 9 (IGE9) [MIM:607682]. IGE9 is characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain.
O00305	Genetic variations in CACNB4 are the cause of susceptibility to juvenile myoclonic epilepsy type 6 (EJM6) [MIM:607682]. EJM6 is a subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue.
P55291	A chromosomal aberration involving CDH15 and KIRREL3 is found in a patient with severe mental retardation and dysmorphic facial features. Translocation t(11;16)(q24.2;q24).
P55291	Defects in CDH15 are the cause of mental retardation autosomal dominant type 3 (MRD3) [MIM:612580]. Mental retardation is characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.
Q9H251	Defects in CDH23 are the cause of Usher syndrome type 1D (USH1D) [MIM:601067]. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa and sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness.
Q9H251	Defects in CDH23 are a cause of Usher syndrome type 1D/F (USH1DF) [MIM:601067]. USH1DF patients are heterozygous for mutations in CDH23 and PCDH15, indicating a digenic inheritance pattern.
Q9H251	Defects in CDH23 are the cause of non-syndromic sensorineural deafness autosomal recessive type 12 (DFNB12) [MIM:601386]. DFNB12 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Q99PF4	Defects in Cdh23 are the cause of waltzer (v) phenotype. Waltzer mice are characterized by deafness and vestibular dysfunction due to degeneration of the neuroepithelium within the inner ear.
P12830	Defects in CDH1 are a cause of gastric cancer [MIM:137215]; also known as hereditary familial diffuse gastric cancer (HDGC).
P12830	Defects in CDH1 are a cause of susceptibility to endometrial cancer [MIM:608089].
P12830	Defects in CDH1 are associated with ovarian cancer [MIM:167000]. Ovarian cancer is the leading cause of death from gynecologic malignancy. It is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases. These typical features relate to the biology of the disease, which is a principal determinant of outcome.
P22223	Defects in CDH3 are the cause of hypotrichosis with juvenile macular dystrophy (HJMD) [MIM:601553]. HJMD is a rare autosomal recessive disorder characterized by early hair loss heralding severe degenerative changes of the retinal macula and culminating in blindness during the second to third decade of life.
P22223	Defects in CDH3 are the cause of ectodermal dysplasia with ectrodactyly and macular dystrophy (EEM) [MIM:225280]; also known as EEM syndrome, Albrectsen-Svendsen syndrome or Ohdo- Hirayama-Terawaki syndrome. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EEM is an autosomal recessive condition characterized by features of ectodermal dysplasia such as sparse eyebrows and scalp hair, and selective tooth agenesis associated with macular dystrophy and ectrodactyly.
P00918	Defects in CA2 are the cause of autosomal recessive osteopetrosis type 3 (OPTB3) [MIM:259730]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.
P22748	Defects in CA4 are the cause of retinitis pigmentosa type 17 (RP17) [MIM:600852]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP17 inheritance is autosomal dominant.
Q9HC91	Genetic variations in CAPN10 are associated with susceptibility to non-insulin-dependent diabetes mellitus type 1 (NIDDM1) [MIM:601283]. Diabetes mellitus is a heterogeneous group of metabolic diseases characterized by high blood glucose levels which, if untreated, lead to blindness, kidney and heart disease, stroke, loss of limbs and reduced life expectancy. Diabetes mellitus can be divided into two main types, type 1 or insulin- dependent diabetes mellitus, and type 2 or non insulin-dependent diabetes mellitus (NIDDM) [MIM:125853]. NIDDM normally starts in adulthood and is characterized by defects in insulin action and insulin secretion.
P20807	Defects in CAPN3 are the cause of limb-girdle muscular dystrophy type 2A (LGMD2A) [MIM:253600]. LGMD2A is an autosomal recessive degenerative myopathy characterized by progressive symmetrical atrophy and weakness of the proximal limb muscles and elevated serum creatine kinase. The symptoms usually begin during the first two decades of life, and the disease gradually worsens, often resulting in loss of walking ability 10 or 20 years after onset.
Q8NG31	A chromosomal aberration involving CASC5 is associated with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14) with MLL/HRX. May give rise to a MLL-CASC5 fusion protein.
Q96T22	Defects in CASP8 are the cause of caspase-8 deficiency (CASP8D) [MIM:607271]. CASP8D is a disorder resembling autoimmune lymphoproliferative syndrome (ALPS). It is characterized by lymphadenopathy, splenomegaly, and defective CD95-induced apoptosis of peripheral blood lymphocytes (PBLs). It leads to defects in activation of T-lymphocytes, B-lymphocytes, and natural killer cells leading to immunodeficiency characterized by recurrent sinopulmonary and herpes simplex virus infections and poor responses to immunization.
Q92851	Defects in CASP10 are the cause of autoimmune lymphoproliferative syndrome type 2A (ALPS2A) [MIM:603909]. ALPS2 is characterized by abnormal lymphocyte and dendritic cell homeostasis and immune regulatory defects.
Q92851	Defects in CASP10 are a cause of familial non-Hodgkin lymphoma (NHL) [MIM:605027]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss.
Q92851	Defects in CASP10 are a cause of gastric cancers [MIM:137215].
O14958	Defects in CASQ2 are the cause of catecholaminergic polymorphic ventricular tachycardia type 2 (CPVT2) [MIM:611938]; also known as stress-induced polymorphic ventricular tachycardia (VTSIP). CPVT2 is an autosomal recessive form of arrhythmogenic disorder characterized by stress-induced, bidirectional ventricular tachycardia that may degenerate into cardiac arrest and cause sudden death.
P41180	Defects in CASR are the cause of familial hypocalciuric hypercalcemia type 1 (FHH) [MIM:145980]. FHH is characterized by altered calcium homeostasis. Affected individuals exhibit mild or modest hypercalcemia, relative hypocalciuria, and inappropriately normal PTH levels.
P41180	Defects in CASR are the cause of neonatal severe primary hyperparathyroidism (NSHPT) [MIM:239200]. NSHPT is a rare autosomal recessive life-threatening disorder characterized by very high serum calcium concentrations, skeletal demineralization, and parathyroid hyperplasia. In some instances NSHPT has been demonstrated to be the homozygous form of FHH.
P41180	Defects in CASR are a cause of familial isolated hypoparathyroidism (FIH) [MIM:146200]; also called autosomal dominant hypoparathyroidism or autosomal dominant hypocalcemia. FIH is characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Symptoms are seizures, tetany and cramps. An autosomal recessive form of FIH also exists.
P41180	Defects in CASR are the cause of idiopathic generalized epilepsy type 8 (IGE8) [MIM:612899]; also known as EIG8. A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Seizure types are variable, but include myoclonic seizures, absence seizures, febrile seizures, complex partial seizures, and generalized tonic-clonic seizures.
O97492	Defects in CAT are the cause of acatalasia; also known as acatalasemia. This disease is characterized by absence of catalase activity.
P04040	Defects in CAT are the cause of acatalasia (ACATLAS) [MIM:115500]; also known as acatalasemia. This disease is characterized by absence of catalase activity in red cells and is often associated with ulcerating oral lesions.
Q8WYA8	Defects in CTSC are a cause of Papillon-Lefevre syndrome (PLS) [MIM:245000]; also known as keratosis palmoplantaris with periodontopathia. PLS is an autosomal recessive disorder characterized by palmoplantar keratosis and severe periodontitis affecting deciduous and permanent dentitions and resulting in premature tooth loss. The palmoplantar keratotic phenotype vary from mild psoriasiform scaly skin to overt hyperkeratosis. Keratosis also affects other sites such as elbows and knees.
Q8WYA8	Defects in CTSC are a cause of Haim-Munk syndrome (HMS) [MIM:245010]; also known as keratosis palmoplantaris with periodontopathia and onychogryposis or Cochin Jewish disorder. HMS is an autosomal recessive disorder characterized by palmoplantar keratosis, onychogryphosis and periodontitis. Additional features are pes planus, arachnodactyly, and acroosteolysis.
Q8WYA8	Defects in CTSC are a cause of juvenile periodontitis (JPD) [MIM:170650]; also known as prepubertal periodontitis (PPP). JPD is characterized by severe and protracted gingival infections, leading to tooth loss. JPD inheritance is autosomal dominant.
P07339	Defects in CTSD are the cause of neuronal ceroid lipofuscinosis type 10 (CLN10) [MIM:610127]; also known as neuronal ceroid lipofuscinosis due to cathepsin D deficiency. A form of neuronal ceroid lipofuscinosis with onset at birth or early childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy.
Q9MZS8	Defects in CTSD are a cause of congenital ovine neuronal ceroid lipofuscinosis (CONCL). CONCL is an autosomal recessive disorder. Newborn lambs are weak, trembling, and unable to rise and support their bodies. However, they are able to vocalize, support their heads, and to suckle if bottle-fed. At autopsy, the brains of affected lambs are strikingly small. The deep layers of the cerebral cortex show pronounced neuronal loss, reactive astrocytosis, and infiltration of macrophages. There is severe degeneration of hippocampal pyramidal neurons.
P43235	Defects in CTSK are the cause of pycnodysostosis (PKND) [MIM:265800]. PKND is an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature.
Q03135	Defects in CAV1 are the cause of congenital generalized lipodystrophy type 3 (CGL3) [MIM:612526]; also called Berardinelli-Seip congenital lipodystrophy type 3 (BSCL3). Congenital generalized lipodystrophies are autosomal recessive disorders characterized by a near absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes.
P56539	Defects in CAV3 are the cause of limb-girdle muscular dystrophy type 1C (LGMD1C) [MIM:607801]. LGMD1C is a myopathy characterized by calf hypertrophy and mild to moderate proximal muscle weakness. LGMD1C inheritance can be autosomal dominant or recessive.
P56539	Defects in CAV3 are a cause of hyperCKmia [MIM:123320]. It is a disease characterized by persistent elevated levels of serum creatine kinase without muscle weakness.
P56539	Defects in CAV3 are a cause of rippling muscle disease (RMD) [MIM:606072]. RMD is a rare disorder characterized by mechanically triggered contractions of skeletal muscle. In RMD, mechanical stimulation leads to electrically silent muscle contractions that spread to neighboring fibers that cause visible ripples to move over the muscle.
P56539	Defects in CAV3 are a cause of cardiomyopathy familial hypertrophic (CMH) [MIM:192600]; also designated FHC or HCM. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
P56539	Defects in CAV3 are the cause of long QT syndrome type 9 (LQT9) [MIM:611818]. Long QT syndromes are heart disorders characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to excercise or emotional stress. They can present with a sentinel event of sudden cardiac death in infancy.
P56539	Defects in CAV3 can be a cause of sudden infant death syndrome (SIDS) [MIM:272120]. SIDS is the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of clinical history. Pathophysiologic mechanisms for SIDS may include respiratory dysfunction, cardiac dysrhythmias, cardiorespiratory instability, and inborn errors of metabolism, but definitive pathogenic mechanisms precipitating an infant sudden death remain elusive. Long QT syndromes-associated mutations can be responsible for some SIDS cases.
P08185	Defects in SERPINA6 are a cause of corticosteroid-binding globulin deficiency (CBG deficiency) [MIM:611489]. CBG deficiency is an extremely rare hereditary disorder characterized by reduced corticosteroid-binding capacity with normal or low plasma corticosteroid-binding globulin concentration, and normal or low basal cortisol levels associated with hypo/hypertension and muscle fatigue.
Q8K4S7	Lack of Cblb expression is the cause of the Komeda diabetes-prone (KDP) phenotype, characterized by autoimmune destruction of pancreatic beta cells and rapid onset of overt diabetes with no sex difference and no significant T-cell lymphopenia. The KPD rat is a spontaneous animal model for human type 1 diabetes mellitus.
P22682	Can be converted to an oncogenic protein by deletions or mutations that disturb its ability to down-regulate RTKs.
Q8N4T0	A chromosomal aberration involving CPA6 was found in a patient with Duane retraction syndrome (DURS) [MIM:126800]. Translocation t(6;8)(q26;q13).
Q641K1	Defects in Agtpbp1 are a cause of Purkinje cell degeneration (pcd). The classical recessive mouse mutant, Purkinje cell degeneration (pcd), exhibits adult-onset degeneration of cerebellar Purkinje neurons, retinal photoreceptors, olfactory bulb mitral neurons, and selected thalamic neurons, and has defective spermatogenesis.
Q00493	Defects in Cpe are the cause of the fat phenotype. Mice homozygous for the fat mutation develop obesity and hyperglycemia that can be suppressed by treatment with exogenous insulin.
P15169	Defects in CPN1 are the cause of carboxypeptidase N deficiency [MIM:212070]. Patients affected present some combination of angioedema or chronic urticaria, as well as hay fever or astma, and have also slightly depressed serum carboxy peptidase N, suggestive of autosomal recessive inheritance of this disorder.
Q92793	Chromosomal aberrations involving CREBBP may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with MYST3/MOZ; translocation t(11;16)(q23;p13.3) with MLL/HRX; translocation t(10;16)(q22;p13) with MYST4/MORF. MYST3-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription.
Q92793	Defects in CREBBP are a cause of Rubinstein-Taybi syndrome (RSTS) [MIM:180849]. RSTS is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.
P35520	Defects in CBS are the cause of cystathionine beta- synthase deficiency (CBSD) [MIM:236200]. It is a recessively inherited error of sulfur amino acid metabolism leading to homocystinuria. Homocystinuria is associated with elevated levels of homocysteine in the blood (homocysteinemia) [MIM:603174]. Patients with homocystinuria have also methionine in their body fluid and usually benefit from dietary and pharmacological treatment (high doses of pyridoxine and vitamin B6). Other characteristics are dislocated optic lenses, vascular disorders (arteriosclerosis and thrombosis), skeletal abnormalities, and mental retardation.
P84444	Mice carrying an autosomal recessive mutation designated paucity of lymph node T-cells (plt) show dramatically reduced numbers of T-cells in lymph nodes, Peyer patches, and the white pulp of the spleen. Plt seems to correspond to Scya21b.
Q96HJ3	A chromosomal aberration involving CCDC34 is found in a patient with hamartoma of the retinal pigment epithelium and retina. Translocation t(11;18) (p13;p11.2).
Q8IVM0	Defects in CCDC50 are the cause of autosomal dominant non-syndromic sensorineural deafness type 44 (DFNA44) [MIM:607453]. The hearing loss is initially moderate and affects mainly low to mid frequencies. Later, it progresses to involve all the frequencies and leads to a profound hearing loss by the 6th decade. The onset of the hearing loss occurs in the first decade of life.
Q16204	A chromosomal aberration involving CCDC6 is a cause of thyroid papillary carcinoma (PACT) [MIM:188550]. Inversion inv(10)(q11.2;q21) generates the RET/CCDC6 (PTC1) oncogene.
O88602	Defects in Cacng2 cause the stargazer (stg) phenotype. Stg mice have spike-wave seizures characteristic of absence epilepsy, with accompanying defects in the cerebellum and inner ear.
P53701	Defects in HCCS are a cause of microphthalmia syndromic type 7 (MCOPS7) [MIM:309801]; also known as microphthalmia with linear skin defects (MLS) or MIDAS syndrome. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye TO complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS7 is a disorder characterized by unilateral or bilateral microphthalmia, linear skin defects in affected females, and in utero lethality for males. Skin defects are limited to the face and neck, consisting of areas of aplastic skin that heal with age to form hyperpigmented areas. Additional features in female patients include agenesis of the corpus callosum, sclerocornea, chorioretinal abnormalities, infantile seizures, congenital heart defect, mental retardation, and diaphragmatic hernia.
Q9BSQ5	Defects in CCM2 are the cause of cerebral cavernous malformations type 2 (CCM2) [MIM:603284]. Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the central nervous system that can result in hemorrhagic stroke, seizures, recurrent headaches, and focal neurologic deficits. CCMs have an incidence of 0.1%-0.5% in the general population and are usually present clinically during the 3rd to 5th decades of life. The lesions are characterized by grossly enlarged blood vessels consisting of a single layer of endothelium and without any intervening neural tissue, ranging in diameter from a few millimeters to several centimeters.
P24385	A chromosomal aberration involving CCND1 may be a cause of B-lymphocytic malignancy, particularly mantle-cell lymphoma (MCL). Translocation t(11;14)(q13;q32) with immunoglobulin gene regions. Activation of CCND1 may be oncogenic by directly altering progression through the cell cycle.
P24385	A chromosomal aberration involving CCND1 may be a cause of parathyroid adenomas [MIM:168461]. Translocation t(11;11)(q13;p15) with the parathyroid hormone (PTH) enhancer.
P24385	A chromosomal aberration involving CCND1 may be a cause of multiple myeloma [MIM:254500]. Translocation t(11;14)(q13;q32) with the IgH locus.
O14708	Genetic variation in CCR5 is associated with suseptibility to insulin-dependent diabetes mellitus type 22 (IDDM22) [MIM:612522]. IDDM is caused by the body's own immune system which destroys the insulin-producing beta cells in the pancreas. Classical features are polydipsia, polyphagia and polyuria, due to hyperglycemia-induced osmotic diuresis.
P48509	Defects in CD151 are the cause of nephropathy with pretibial epidermolysis bullosa and deafness (NPEBD) [MIM:609057]. NPEBD is characterized by the association of hereditary nephritis, epidermolysis bullosa, deafness, and beta-thalassemia minor.
P15391	Defects in CD19 are a cause of hypogammaglobulinemia [MIM:107265].
P25063	Genetic variations in CD24 are involved in multiple sclerosis susceptibility (MS) [MIM:126200]. MS is a neurodegenerative disorder characterized by the gradual accumulation of focal plaques of demyelination particularly in the periventricular areas of the brain. Peripheral nerves are not affected. Onset usually in third or fourth decade with intermittent progression over an extended period. The cause is still uncertain.
P42771	Genetic variations in CDKN2A may underlie susceptibility to uveal melanoma [MIM:155720]. Uveal melanoma is the most common type of ocular malignant tumor, consisting of overgrowth of uveal melanocytes and often preceded by a uveal nevus.
P42771	Defects in CDKN2A are the cause of cutaneous malignant melanoma 2 (CMM2) [MIM:155601]. Inheritance is autosomal dominant. Malignant melanoma is a malignant neoplasm of melanocytes, arising de novo or from a preexisting benign nevus, which occurs most often in the skin but also may involve other sites.
P42771	Defects in CDKN2A are the cause of familial atypical multiple mole melanoma-pancreatic carcinoma syndrome (FAMMMPC) [MIM:606719].
P42771	Defects in CDKN2A are a cause of Li-Fraumeni syndrome (LFS) [MIM:151623]. LFS is a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53.
P42771	Defects in CDKN2A are the cause of melanoma-astrocytoma syndrome [MIM:155755]. The melanoma-astrocytoma syndrome is characterized by a dual predisposition to melanoma and neural system tumors, commonly astrocytoma.
Q9Y5K6	Defects in CD2AP are the cause of susceptibility to focal segmental glomerulosclerosis 3 (FSGS3) [MIM:607832]. FSGS3 is a common renal lesion characterized by increased urinary protein excretion and decreasing kidney function. Renal insufficiency often progresses to end-stage renal failure, a highly morbid state requiring either dialysis therapy or kidney transplantation. FSGS is defined by the presence of segmental sclerosis in glomeruli, and is seen in all ethnic groups, although it is particularly common in individuals of African descent. FSGS occurs as an isolated primary condition or secondary to disorders as HIV infection, obesity, hypertension and diabetes. FSGS may also be inherited as a mendelian trait.
Q9BZN4	Defects in CD36 are the cause of platelet glycoprotein IV deficiency [MIM:608404]; also known as CD36 deficiency. Platelet glycoprotein IV deficiency can be divided into 2 subgroups. The type I phenotype is characterized by platelets and monocytes/macrophages exhibiting complete CD36 deficiency. The type II phenotype lacks the surface expression of CD36 in platelets, but expression in monocytes/macrophages is near normal.
Q9BZN4	Genetic variations in CD36 are associated with susceptibility to coronary heart disease type 7 (CHDS7) [MIM:610938].
P04234	Defects in CD3D are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell- positive/NK-cell-positive (T(-)/B(+)/NK(+) SCID) [MIM:608971]. A form of severe combined immunodeficiency (SCID), a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T-cell development.
P20963	Defects in CD247 are a cause of primary T-cell immunodeficiency [MIM:610163]. Affected individuals suffer of recurrent infections. Patients T-cell counts are very low and B- cell counts are normal.
P29965	Defects in CD40LG are the cause of X-linked immunodeficiency with hyper-IgM type 1 (HIGM1) [MIM:308230]; also known as X-linked hyper IgM syndrome (XHIM). HIGM1 is an immunoglobulin isotype switch defect characterized by elevated concentrations of serum IgM and decreased amounts of all other isotypes. Affected males present at an early age (usually within the first year of life) recurrent bacterial and opportunistic infections, including Pneumocystis carinii pneumonia and intractable diarrhea due to cryptosporidium infection. Despite substitution treatment with intravenous immunoglobulin, the overall prognosis is rather poor, with a death rate of about 10% before adolescence.
P13987	Defects in CD59 are the cause of CD59 deficiency [MIM:612300].
P11912	Defects in CD79A are a cause of non-Bruton type agammaglobulinemia [MIM:601495]. Agammaglobulinemia is an immunodeficiency disease which results in developmental defects in the maturation pathway of B-cells. Two different mutations, one at the splice donor site of intron 2 and the other at the splice acceptor site for exon 3, have been identified. Both mutations give rise to a truncated protein.
P40259	Defects in CD79B are a cause of hypogammaglobulinemia immunodeficiency and reduced B cells [MIM:612692]. Hypogammaglobulinemia is an immunologic deficiency state characterized by an extremely low level of generally all classes of gamma-globulin in the blood. The disorder results in a failure of B cell development in patients with immunodeficiency and is associated with a markedly reduced but not absent B cells.
P01732	Defects in CD8A are a cause of familial CD8 deficiency (CD8 deficiency) [MIM:608957]. Familial CD8 deficiency is a novel autosomal recessive immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections.
Q8IWY9	Defects in CDAN1 are the cause of congenital dyserythropoietic anemia type 1 (CDA1) [MIM:224120]. An autosomal recessive blood disorder characterized by morphological abnormalities of erythroblasts, ineffective erythropoiesis, macrocytic anemia and secondary hemochromatosis. It is occasionally associated with bone abnormalities, especially of the hands and feet (acrodysostosis), nail hypoplasia, and scoliosis. Ultrastructural features include internuclear chromatin bridges connecting some nearly completely separated erythroblasts and an abnormal appearance (spongy or Swiss-cheese appearance) of the heterochromatin in a high proportion of the erythroblasts.
Q99459	A chromosomal aberration involving CDC5L is found in multicystic renal dysplasia. Translocation t(6;19)(p21;q13.1) with USF2.
Q6P1J9	Defects in CDC73 are a cause of familial isolated hyperparathyroidism (FIHP) [MIM:145000]; also known as hyperparathyroidism type 1 (HRPT1). FIHP is an autosomal dominant disorder characterized by hypercalcemia, elevated parathyroid hormone (PTH) levels, and uniglandular or multiglandular parathyroid tumors.
Q6P1J9	Defects in CDC73 are the cause of hyperparathyroidism-jaw tumor syndrome (HPT-JT) [MIM:145001]; also known as hyperparathyroidism type 2 (HRPT2) or familial primary hyperparathyroidism with multiple ossifying jaw fibromas. HPT-JT is an autosomal dominant, multiple neoplasia syndrome primarily characterized by hyperparathyroidism due to parathyroid tumors. Thirty percent of individuals with HPT-JT may also develop ossifying fibromas, primarily of the mandible and maxilla, which are distinc from the brown tumors associated with severe hyperparathyroidism. Kidney lesions may also occur in HPT-JT as bilateral cysts, renal hamartomas or Wilms tumors.
Q6P1J9	Defects in CDC73 are a cause of parathyroid carcinoma [MIM:608266]. These cancers characteristically result in more profound clinical manifestations of hyperparathyroidism than do parathyroid adenomas, the most frequent cause of primary hyperparathyroidism. Early en bloc resection of the primary tumor is the only curative treatment.
P11802	CDK4 mutations are involved in tumor formation.
P11802	Defects in CDK4 are the cause of cutaneous malignant melanoma 3 (CMM3) [MIM:609048, 155600]. Malignant melanoma is a malignant neoplasm of melanocytes, arising de novo or from a preexisting benign nevus, which occurs most often in the skin but also may involve other sites.
O76039	Chromosomal aberrations involving CDKL5 are found in patients manifesting early-onset seizures and spams and psychomotor impairment. Translocation t(X;6)(p22.3;q14); translocation t(X;7)(p22.3;p15).
O76039	Defects in CDKL5 are a cause of epileptic encephalopathy early infantile type 2 (EIEE2) [MIM:300672]; also known as atypical CDKL5-related Rett syndrome. EIEE2 is a severe form of epilepsy characterized by seizures or spasms beginning in infancy. Patients manifest features resembling Rett syndrome such as microcephaly, lack of speech development, stereotypic hand movements.
Q9C046	Defects in CDKN3 are found in patients with hepatocellular carcinoma (HCC) [MIM:114550].
P46527	Defects in CDKN1B are the cause of multiple endocrine neoplasia type 4 (MEN4) [MIM:610755]. Multiple endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 and MEN2.
P49918	Defects in CDKN1C are a cause of Beckwith-Wiedemann syndrome (BWS) [MIM:130650]. BWS is a genetically heterogeneous disorder characterized by anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumors.
P49918	Defects in CDKN1C are involved in tumor formation.
Q9UIN7	Defects in CDSN are a cause of hypotrichosis simplex of the scalp (HTSS) [MIM:146520]; also known as hypotrichosis Spanish type. HTSS is an autosomal dominant form of isolated alopecia. Affected individuals have normal hair in early childhood but experience progressive loss of scalp hair beginning in the middle of the first decade and almost complete baldness by the third decade.
O15078	Defects in CEP290 are a cause of Joubert syndrome type 5 (JBTS5) [MIM:610188]. Joubert syndrome is an autosomal recessive disease characterized by cerebellar vermis hypoplasia with prominent superior cerebellar peduncles (the 'molar tooth sign' on axial magnetic resonance imaging), psychomotor delay, hypotonia, ataxia, oculomotor apraxia and neonatal breathing abnormalities. JBTS5 shares the neurologic and neuroradiologic features of Joubert syndrome together with severe retinal dystrophy and/or progressive renal failure characterized by nephronophthisis.
O15078	Defects in CEP290 are a cause of Senior-Loken syndrome type 6 (SLSN6) [MIM:610189]. Senior-Loken syndrome is also known as juvenile nephronophthisis with Leber amaurosis. It is an autosomal recessive renal-retinal disorder, characterized by progressive wasting of the filtering unit of the kidney, with or without medullary cystic renal disease, and progressive eye disease.
O15078	Defects in CEP290 are the cause of Leber congenital amaurosis type 10 (LCA10) [MIM:611755]. LCA designates a clinically and genetically heterogeneous group of childhood retinal degenerations, generally inherited in an autosomal recessive manner. Affected infants have little or no retinal photoreceptor function as tested by electroretinography. LCA represents the most common genetic cause of congenital visual impairment in infants and children.
O15078	Defects in CEP290 are the cause of Meckel syndrome type 4 (MKS4) [MIM:611134]. MKS4 is an autosomal recessive disorder characterized by a combination of renal cysts and variably associated features including developmental anomalies of the central nervous system (typically encephalocele), hepatic ductal dysplasia and cysts, and polydactyly.
O15078	Antibodies against CEP290 are present in sera from patients with cutaneous T-cell lymphomas, but not in the healthy control population.
Q6A078	Defects in Cep290 are a cause of early-onset retinal degeneration with autosomal recessive inheritance. The rd16 mutant carries a deletion of residues 1599-1897 in the Cep290 protein. Homozygous rd16 mice are characterized by the appearance of white retinal vessels at 1 month of age and large pigment patches at 2 months. Retinal degeneration is apparent as early as postnatal day 19 and progresses with age. The rd16 retina exhibits altered disitribution of Rpgr and phototransduction proteins within the photoreceptor cells.
P19835	Defects in CEL are a cause of maturity-onset diabetes of the young type 8 with exocrine dysfunction (MODY8) [MIM:609812]; also known as diabetes and pancreatic exocrine dysfunction (DPED). MODY [MIM:606391] is an autosomal dominant form of diabetes mellitus. The pancreas serves both endocrine and exocrine functions. The endocrine cells are found in the islets of Langerhans. They synthesize insulin and other hormones, and are involved in the pathogenesis of diabetes mellitus. The exocrine cells produce bicarbonate and digestive enzymes and are involved in the pathogenesis of pancreatic malabsorption. The localization of the islets within exocrine pancreatic tissue is suggestive of an interdependency and cross-talk between these two cell populations in their normal and in their abnormal function.
Q9HC77	Defects in CENPJ are the cause of microcephaly primary type 6 (MCPH6) [MIM:608393]. A disorder defined as a head circumference more than 3 standard deviations below the age- related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits.
Q9BS16	Chromosomal aberrations involving CENPK are a cause of acute leukemias. Translocation t(5;11)(q12;q23) with MLL.
Q5DVJ5	Defects in CERKL are the cause of retinitis pigmentosa type 26 (RP26) [MIM:608380]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP26 inheritance is autosomal recessive.
P00450	Defects in CP are the cause of aceruloplasminemia (ACERULOP) [MIM:604290]. It is an autosomal recessive disorder of iron metabolism characterized by iron accumulation in the brain as well as visceral organs. Clinical features consist of the triad of retinal degeneration, diabetes mellitus and neurological disturbances.
P00450	Ceruloplasmin levels are decreased in Wilson disease, in which copper cannot be incorporated into ceruloplasmin in liver because of defects in the copper-transporting ATPase 2.
P11597	Defects in CETP are a cause of hyperalphalipoproteinemia [MIM:143470]. Affected individuals show high levels of alpha- lipoprotein (high density lipoprotein/HDL).
P11597	Defects in CETP are the cause of CETP deficiency [MIM:607322]. This is an autosomal dominant condition associated with increased HDL cholesterol levels.
P00746	Defects in CFD are the cause of complement factor D deficiency [MIM:134350]. This deficiency predisposes to invasive meningococcal disease.
Q9NU86	Genetic variations in CFH are associated with basal laminar drusen [MIM:126700]; also known as drusen of Bruch membrane or cuticular drusen or grouped early adult-onset drusen. Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. Basal laminar drusen refers to an early adult-onset drusen phenotype that shows a pattern of uniform small, slightly raised yellow subretinal nodules randomly scattered in the macula. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss.
Q9NU86	Defects in CFH are the cause of complement factor H deficiency (CFH deficiency) [MIM:609814]. CFH deficiency determines uncontrolled activation of the alternative complement pathway with consumption of C3 and often other terminal complement components. It is associated with a number of renal diseases with variable clinical presentation and progression, including membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome. CFH deficiency patients may show increased susceptibility to meningococcal infections.
Q9NU86	Defects in CFH are a cause of hemolytic-uremic syndrome (HUS) [MIM:235400]. HUS is a microvasculature disorder leading to microangiopathic hemolytic anemia associated with distorted erythrocytes ('burr cells'), thrombocytopenia, and acute renal failure. Both dominant and recessive modes of inheritance have been reported. Most cases of HUS are associated with epidemics of diarrhea caused by verocytotoxin-producing bacteria, but atypical cases of HUS not associated with diarrhea (aHUS) also occur.
Q9NU86	Genetic variation in CFH is associated with age-related macular degeneration type 4 (ARMD4) [MIM:610698]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin- containing structure known as Bruch membrane.
P05156	Defects in CFI are the cause of component I deficiency (CFI deficiency) [MIM:217030]. CFI deficiency is an autosomal recessive condition associated with a propensity to pyogenic infections.
P05156	Defects in CFI may be associated with or predispose to hemolytic uraemic syndrome (HUS) [MIM:235400]. HUS, the most frequent cause of acute renal failure in childhood, is characterized by the association of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. The majority of HUS cases occur after an episode of infectious diarrhea, and are associated with E.coli O157:H7 infection. However, atypical cases of HUS occur in the absence of infectious diarrhea, although less commonly. Some are inherited in either an autosomal dominant or a recessive pattern and these patients often experience relapse and progress to hypertension and chronic renal disease. Sporadic forms can occur with many of the same signs and symptoms.
P05156	Defects in CFI are the cause of complement factor I deficiency (CFI deficiency) [MIM:610984]. CFI deficiency is an autosomal recessive condition associated with a propensity to pyogenic infections.
Q9GZR3	Defects in CFC1 are the cause of visceral heterotaxy autosomal type 2 (HTX2) [MIM:605376]. A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. It results in an abnormal arrangement of visceral organs, and a wide variety of congenital defects including cardiac malformations and situs inversus or situs ambiguus.
Q9GZR3	Defects in CFC1 are a cause of transposition of the great arteries, dextro-looped (DTGA) [MIM:608808]. The more common form of DTGA, consists of complete inversion of the great vessels, so that the aorta incorrectly arises from the right ventricle and the pulmonary artery incorrectly arises from the left ventricle. This creates completely separate pulmonary and systemic circulatory systems, an arrangement that is incompatible with life. Patients often have atrial and/or ventricular septal defects or other types of shunting that allow some mixing between the circulations in order to support life minimally, but surgical intervention is always required.
Q9GZR3	Defects in CFC1 are a cause of conotruncal heart malformations (CTHM) [MIM:217095]. CTHM consist of cardiac outflow tract defects, such as tetralogy of Fallot, pulmonary atresia, double-outlet right ventricle, truncus arteriosus communis, and aortic arch anomalies.
P13569	Defects in CFTR are the cause of cystic fibrosis (CF) [MIM:219700]; also known as mucoviscidosis. CF is the most common genetic disease in the Caucasian population, with a prevalence of about 1 in 2'000 live births. Inheritance is autosomal recessive. CF is a common generalized disorder of exocrine gland function which impairs clearance of secretions in a variety of organs. It is characterized by the triad of chronic bronchopulmonary disease (with recurrent respiratory infections), pancreatic insufficiency (which leads to malabsorption and growth retardation) and elevated sweat electrolytes.
P13569	Defects in CFTR are the cause of congenital bilateral absence of the vas deferens (CBAVD) [MIM:277180]. CBAVD is an important cause of sterility in men and could represent an incomplete form of cystic fibrosis, as the majority of men suffering from cystic fibrosis lack the vas deferens.
Q9HAC7	Defects in C7orf10 are the cause of glutaric aciduria type 3 (GA3) [MIM:231690]. GA3 is a metabolic disorder due to peroxisomal glutaryl-CoA oxidase deficiency and characterized by the excretion of abnormal quantities of glutaric acid but low 3- hydroxyglutaric acid.
P32929	Defects in CTH are the cause of cystathioninuria [MIM:219500]. CTH is an autosomal recessive phenotype characterized by abnormal accumulation of plasma cystathionine, leading to increased urinary excretion.
Q0VF96	A chromosomal aberration involving CGNL1 is a cause of aromatase excess syndrome [MIM:139300]. This is characterized by an estrogen excess due to an increased aromatase activity. An inversion on inv(15)(q21.2;q21.3) moves the promoter of the CGNL1 gene into a 5-prime position in relation to the aromatase coding region.
Q330K2	Defects in C8orf38 are a cause of complex I mitochondrial respiratory chain deficiency [MIM:252010]. Complex I (NADH- ubiquinone oxidoreductase), the largest complex of the mitochondrial respiratory chain, contains more than 40 subunits. It is embedded in the inner mitochondrial membrane and is partly protruding in the matrix. Complex I deficiency is the most common cause of mitochondrial disorders. It represents largely one-third of all cases of respiratory chain deficiency and is responsible for a variety of clinical symptoms, ranging from neurological disorders to cardiomyopathy, liver failure, and myopathy.
P36222	A genetic variation in CHI3L1 is associated with susceptibility to asthma-related traits type 7 (ASRT7) [MIM:611960]. Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing and dyspnea, bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test, serum IgE levels, atopy, and atopic dermatitis.
P10809	Defects in HSPD1 are a cause of spastic paraplegia autosomal dominant type 13 (SPG13) [MIM:605280]. Spastic paraplegia is a degenerative spinal cord disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs.
P10809	Defects in HSPD1 are the cause of leukodystrophy hypomyelinating type 4 (HLD4) [MIM:612233]; also called mitochondrial HSP60 chaperonopathy or MitCHAP-60 disease. HLD4 is a severe autosomal recessive hypomyelinating leukodystrophy. Clinically characterized by infantile-onset rotary nystagmus, progressive spastic paraplegia, neurologic regression, motor impairment, profound mental retardation. Death usually occurrs within the first two decades of life.
Q9BUK0	A chromosomal aberration involving CHCHD7 may be a cause of salivary gland pleiomorphic adenomas (PA) [181030]. Pleiomorphic adenomas are the most common benign epithelial tumors of the salivary gland. Translocation t(6;8)(p21.3-22;q13) with PLAG1.
Q9P2D1	Defects in CHD7 are a cause of CHARGE syndrome [MIM:214800]. This syndrome, which is a common cause of congenital anomalies, is characterized by a non-random pattern of congenital anomalies including choanal atresia and malformations of the heart, inner ear, and retina.
Q9P2D1	Genetic variations in CHD7 are associated with susceptibility to idiopathic scoliosis type 3 (IS3) [MIM:608765]. Idiopathic scoliosis (IS) is the most common spinal deformity in children.
Q9P2D1	Defects in CHD7 are the cause of Kallmann syndrome type 5 (KAL5) [MIM:612370]. Kallmann syndrome is a disorder that associates hypogonadotropic hypogonadism and anosmia. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone- synthesizing neurons. In some patients other developmental anomalies can be present, which include renal agenesis, cleft lip and/or palate, selective tooth agenesis, and bimanual synkinesis. In some cases anosmia may be absent or inconspicuous.
Q9P2D1	Defects in CHD7 are a cause of idiopathic hypogonadotropic hypogonadism (IHH) [MIM:146110]. IHH is defined as a deficiency of the pituitary secretion of follicle-stimulating hormone and luteinizing hormone, which results in the impairment of pubertal maturation and of reproductive function.
Q9UKJ5	A chromosomal aberration involving CHIC2 is found in a form of acute myeloid leukemia (AML). Translocation t(4;12)(q12;p13) with ETV6.
P15882	Defects in CHN1 are the cause of Duane retraction syndrome type 2 (DURS2) [MIM:604356]. Duane retraction syndrome is a congenital eye movement disorder characterized by a failure of cranial nerve VI (the abducens nerve) to develop normally, resulting in restriction or absence of abduction, adduction, or both, and narrowing of the palpebral fissure and retraction of the globe on attempted adduction. Undiagnosed in children, it can lead to amblyopia, a permanent uncorrectable loss of vision.
Q9UGF0	Defects in CHEK2 are associated with Li-Fraumeni syndrome 2 (LFS2) [MIM:609265]; a highly penetrant familial cancer phenotype usually associated with inherited mutations in p53/TP53.
Q9UGF0	Defects in CHEK2 are found in some patients with prostate cancer (CaP) [MIM:176807].
Q9UGF0	Defects in CHEK2 are found in some patients with osteosarcoma (OSRC) [MIM:259500].
O55229	Defects in Chkb are a cause of rostrocaudal muscular dystrophy (rmd). The disease is characterized by rapidly progressive muscular dystrophy and neonatal forelimb bone deformity. The dystrophy is only evident in skeletal muscle tissues in an unusual rostral-to-caudal gradient.
P06276	Defects in BCHE are the cause of butyrylcholinesterase deficiency (BChE deficiency) [MIM:177400]. BChE deficiency is a metabolic disorder characterized by prolonged apnoea after the use of certain anesthetic drugs, including the muscle relaxants succinylcholine or mivacurium and other ester local anesthetics. The duration of the prolonged apnoea varies significantly depending on the extent of the enzyme deficiency. BChE deficiency is a multifactorial disorder. The hereditary condition is transmitted as an autosomal recessive trait.
Q9UQN3	Defects in CHMP2B are the cause of frontotemporal dementia, chromosome 3-linked (FTD3) [MIM:600795]. FTD3 is characterized by an onset of dementia in the late 50's initially characterized by behavioral and personality changes including apathy, restlessness, disinhibition and hyperorality, progressing to stereotyped behaviors, non-fluent aphasia, mutism and dystonia, with a marked lack of insight. The brains of individuals with FTD3 have no distinctive neuropathological features. They show global cortical and central atrophy, but no beta-amyloid deposits.
Q9H444	Defects in CHMP4B are the cause of cataract posterior polar type 3 (CTPP3) [MIM:605387]. A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity.
Q7LGC8	Defects in CHST3 are the cause of spondyloepiphyseal dysplasia Omani type (SED Omani type) [MIM:608637]. SED Omani type is an autosomal recessive disorder characterized by normal length at birth but severely reduced adult height (110-130 cm), severe progressive kyphoscoliosis, arthritic changes with joint dislocations, genu valgum, cubitus valgus, mild brachydactyly, camptodactyly, microdontia and normal intelligence. As a consequence of the arthropathy and the contractures, affected individuals develop restricted joint movement.
Q7LGC8	Defects in CHST3 are a cause of humerospinal dysostosis (HSD) [MIM:143095]. HSD is characterized by bifurcation of the ends of the humerus, subluxation in the elbow joints, widened iliac bones, talipes equinovarus and coronal cleft vertebrae. Congenital, progressive heart disease, possibly with fatal outcome, is observed in some patients.
Q9GZX3	Defects in CHST6 are the cause of macular corneal dystrophy (MCD) [MIM:217800]. MCD is an autosomal recessive disease characterized by corneal opacities. Onset occurs in the first decade, usually between ages 5 and 9. The disorder is progressive. Minute, gray, punctate opacities develop. Corneal sensitivity is usually reduced. Painful attacks with photophobia, foreign body sensations, and recurrent erosions occur in most patients. There are different types of MCD: MCD type I, in which there is a virtual absence of sulfated keratan sulfate (KS) in the serum and cornea, as determined by KS-specific antibodies; and MCD type II, in which the normal sulfated KS-antibody response is present in cornea and serum. MCD type I patients usually have a homozygous missense mutation, while MCD type II patients show a large deletion and replacement in the upstream region of CHST6. The only missense mutation for type II is Cys-50, which is heterozygous with a replacement in the upstream region on the other allele of CHST6.
Q9NPF2	A chromosomal aberration involving CHST11 is found in B- cell chronic lymphocytic leukemias. Translocation t(12;14)(q23;q32) with IgH.
Q969X6	Defects in CIRH1A are the cause of North American Indian childhood cirrhosis (NAIC) [MIM:604901]. NAIC is a severe autosomal recessive intrahepatic cholestasis, originally described in Ojibway-Cree children from northwestern Quebec. NAIC typically presents with transient neonatal jaundice, in a child who is otherwise healthy, and progresses to biliary cirrhosis and portal hypertension. Biochemical and histopathological features suggest involvement of the bile ducts rather than of the bile canaliculi. They include elevated gamma glutamyltransferase and alkaline phosphatase levels, and, typically, marked fibrosis around bile ducts. Clinically, NAIC is distinct from other nonsyndromic familial cholestases because of its marked cholangiopathic features and severe degree of fibrosis on liver histology.
Q8N5K1	Defects in CISD2 are the cause of Wolfram syndrome 2 (WFS2) [MIM:604928]. WFS2 is a rare autosomal recessive disorder characterized by characterized by optic atrophy and diabetes mellitus. Other symptoms include the presence of profound upper gastrointestinal ulceration, significant bleeding tendency, defective platelet aggregation with collagen and various neurological symptoms.
Q9UIW9	Defects in CDK5RAP2 are the cause of microcephaly primary type 3 (MCPH3) [MIM:604804]. A disorder defined as a head circumference more than 3 standard deviations below the age- related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. Despite this marked reduction in size, the gyral pattern is relatively well preserved, with no major abnormality in cortical architecture. Primary microcephaly is further defined by the absence of other syndromic features or significant neurological deficits.
Q2KHT3	Defects in CLEC16A might be a cause of insulin-dependent diabetes mellitus (IDDM) [MIM:222100].
P28329	Defects in CHAT are the cause of congenital myasthenic syndrome with episodic apnea (CMSEA) [MIM:254210]; formerly known as familial infantile myasthenia gravis 2 (FIMG2). CMSEA is an autosomal recessive congenital myasthenic syndrome. Patients have myasthenic symptoms since birth or early infancy, negative tests for anti-AChR antibodies, and abrupt episodic crises with increased weakness, bulbar paralysis, and apnea precipitated by undue exertion, fever, or excitement.
Q9UBD9	Defects in CLCF1 are the cause of cold-induced sweating syndrome type 2 (CISS2) [MIM:610313]. Cold-induced sweating syndrome (CISS) is an autosomal recessive disorder characterized by profuse sweating induced by cool surroundings (temperatures of 7 to 18 degrees Celsius). Additional abnormalities include a high- arched palate, nasal voice, depressed nasal bridge, inability to fully extend the elbows and kyphoscoliosis.
P51801	Defects in CLCNKB are the cause of Bartter syndrome type 3 (BS3) [MIM:607364]; also known as classic Bartter syndrome. It is an autosomal recessive form of often severe intravascular volume depletion due to renal salt-wasting associated with low blood pressure, hypokalemic alkalosis, hypercalciuria, and normal serum magnesium levels.
Q9MZT1	Defects in CLCN1 are the cause of autosomal recessive myotonia congenita (MCR). MCR is a disorder of sarcolemmal excitation leading to delayed relaxation of skeletal muscle following contractions. The disease has been identified in the miniature Schnauzer breed.
P35523	Defects in CLCN1 are the cause of autosomal dominant myotonia congenita (MCD) [MIM:160800]; also known as Thomsen disease. MCD is characterized by skeletal muscle stiffness (delayed relaxation), due to membrane hyperexcitability. A variant form of Thomsen disease is myotonia levior that is characterized by milder symptoms, later onset and absence of muscle hypo- and hypertrophy.
P35523	Defects in CLCN1 are the cause of autosomal recessive myotonia congenita (MCR) [MIM:255700]; also known as Becker disease.
P51788	Defects in CLCN2 may be the cause of epilepsy with grand mal seizures on awakening (EGMA) [MIM:607628]. EGMA is a subtype of idiopathic generalized epilepsy (IGE) characterized by generalized tonic-clonic seizures (GTCS) occurring predominantly on awakening. The GTCS can be the only symptom or they can be combined with the other subsyndromes of IGE in childhood or adolescence.
P51788	Defects in CLCN2 are the cause of childhood absence epilepsy type 3 (ECA3) [MIM:607682]. ECA3 is a subtype of idiopathic generalized epilepsy (IGE) characterized by onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3 Hz spike waves on EEG. During adolescence, tonic-clonic and myoclonic seizures develop.
P51788	Defects in CLCN2 are a cause of juvenile absence epilepsy (JAE) [MIM:607631]. JAE is a subtype of idiopathic generalized epilepsy (IGE) characterized by onset occurring around puberty, absence seizures, generalized tonic-clonic seizures (GTCS), GTCS on awakening and myoclonic seizures.
P51795	Defects in CLCN5 are a cause of hypophosphatemic rickets X-linked recessive (XLRH) [MIM:300554]. XLRH is a renal disease belonging to the 'Dent disease complex', a group of disorders characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. The spectrum of phenotypic features is remarkably similar in the various disorders, except for differences in the severity of bone deformities and renal impairment. XLRH patients present with rickets or osteomalacia, hypophosphatemia due to decreased renal tubular phosphate reabsorption, hypercalciuria, and low molecular weight proteinuria. Patients develop nephrocalcinosis with progressive renal failure in adulthood. Female carriers may have asymptomatic hypercalciuria or hypophosphatemia only.
P51795	Defects in CLCN5 are the cause of nephrolithiasis type 2 (NPHL2) [MIM:300009]; also known as Dent disease 1. NPHL2 is an X- linked recessive renal disease belonging to the 'Dent disease complex'. NPHL2 patients manifest hypercalciuria, hypophosphatemia, aminoaciduria, nephrocalcinosis and nephrolithiasis, renal insufficiency leading to renal failure in adulthood, rickets (33% of patients) and osteomalacia.
P51795	Defects in CLCN5 are the cause of nephrolithiasis type 1 (NPHL1) [MIM:310468]; also designated XRN. NPHL1 is an X-linked recessive renal disease belonging to the 'Dent disease complex'. NPHL1 presents with hypercalciuria, nephrocalcinosis, renal stones and renal insufficiency. Patients lack urinary acidification defects, rickets, and osteomalacia.
P51795	Defects in CLCN5 are the cause of low molecular weight proteinuria with hypercalciuria and nephrocalcinosis (LMWPHN) [MIM:308990]. LMWPHN is an X-linked renal disease belonging to the 'Dent disease complex'. Patients tend to have hypercalciuric nephrocalcinosis without rickets or renal failure.
P51798	Defects in CLCN7 are the cause of osteopetrosis autosomal recessive type 4 (OPTB4) [MIM:611490]; also known as infantile malignant osteopetrosis type 2. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood.
P51798	Defects in CLCN7 are a cause of osteopetrosis autosomal dominant type 2 [MIM:166600]; also known as autosomal dominant Albers-Schonberg disease or marble disease autosomal dominant. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. OPTA2 is the most common form of osteopetrosis, occurring in adolescence or adulthood. It is characterized by sclerosis, predominantly involving the spine, the pelvis and the skull base.
O95500	Defects in CLDN14 are the cause of non-syndromic sensorineural deafness autosomal recessive type 29 (DFNB29) [MIM:605608]. DFNB29 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Q9XT98	Defects in CLDN16 are a cause of an autosomal recessive chronic interstitial nephritis with diffuse zonal fibrosis (CINF). CINF is characterized by increased blood urea nitrogen, creatinine, and urinary proteins, leads to lethality before puberty, usually within the first 6 months or year of life.
Q9Y5I7	Defects in CLDN16 are the cause of hypomagnesemia type 3 (HOMG3) [MIM:248250]; also known as familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). HOMG3 is a progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis. Recurrent urinary tract infections and kidney stones are often observed. In spite of hypercalciuria, patients do not show hypocalcemia.
Q8N6F1	Defects in CLDN19 are the cause of hypomagnesemia renal with ocular involvement (HOMGO) [MIM:248190]. HOMGO is a progressive renal disease characterized by primary renal magnesium wasting with hypomagnesemia, hypercalciuria and nephrocalcinosis associated with severe ocular abnormalities such as bilateral chorioretinal scars, macular colobomata, significant myopia and nystagmus. The renal phenotype is virtually undistinguishable from that of patients with HOMG3 with proven CLDN16 mutations.
O95832	Defects in CLDN1 are the cause of ichthyosis-sclerosing cholangitis neonatal syndrome (NISCH) [MIM:607626]; also called ichthyosis with leukocyte vacuoles alopecia and sclerosing cholangitis (ILVASC). NISCH is a rare autosomal recessive complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, vulgar type ichthyosis, and sclerosing cholangitis.
Q8BXK9	Defects in Clic5 are a cause of the jitterbug (jbg) phenotype. Jbg is the result of a spontaneous mutation that leads to severe degeneration of the organ of Corti in the inner ear. Jbg leads to progressive degeneration of inner ear hair cells. Affected mice are identified by head bobbing, circling behavior and their inability to swim. They cannot hear well when young, and become completely deaf after 5 months.
Q9UDT6	Haploinsufficiency of CLIP2 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in Williams-Beuren syndrome (WBS) [MIM:194050]. WBS is a rare developmental disorder. It is a contiguous gene deletion syndrome involving genes from chromosome band 7q11.23.
Q13286	Defects in CLN3 are the cause of neuronal ceroid lipofuscinosis type 3 (CLN3) [MIM:204200]; also known as Batten disease. A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The hallmark of CLN3 is the ultrastructural pattern of lipopigment with a fingerprint profile, which can have 3 different appearances: pure within a lysosomal residual body; in conjunction with curvilinear or rectilinear profiles; and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with CLN3.
Q1ZYR0	Defects in CLN5 are the cause of neuronal ceroid lipofuscinosis (NCL). NCL is characterized by brain atrophy and the accumulation of lysosome derived fluorescent storage bodies in neurons and most other cells. NCL is found in Australian Devon cattle.
Q5JZQ9	Defects in CLN5 are the cause of neuronal ceroid lipofuscinosis (NCL). NCL is characterized by brain atrophy and the accumulation of lysosome derived fluorescent storage bodies in neurons and most other cells. NCL is found in Border collie dogs.
O75503	Defects in CLN5 are the cause of neuronal ceroid lipofuscinosis type 5 (CLN5) [MIM:256731]; also known as Finnish variant late-infantile neuronal ceroid lipofuscinosis (vLINCL). A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment patterns observed most often in neuronal ceroid lipofuscinosis type 5 comprise mixed combinations of granular, curvilinear, and fingerprint profiles.
A2TJ54	Defects in CLN5 are the cause of neuronal ceroid lipofuscinosis (NCL). NCL is characterized by brain atrophy and the accumulation of lysosome derived fluorescent storage bodies in neurons and most other cells. NCL is found in New Zealand Borderdale sheep.
Q9NWW5	Defects in CLN6 are the cause of neuronal ceroid lipofuscinosis type 6 (CLN6) [MIM:601780]. A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment patterns observed most often in neuronal ceroid lipofuscinosis type 6 comprise mixed combinations of granular, curvilinear, and fingerprint profiles.
Q5JZQ7	Defects in CLN8 are a cause of a form of neuronal ceroid lipofuscinosis (NCL) in English setters.
Q9UBY8	Defects in CLN8 are the cause of neuronal ceroid lipofuscinosis type 8 (CLN8) [MIM:600143]. A form of neuronal ceroid lipofuscinosis with onset in childhood. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment patterns observed most often in neuronal ceroid lipofuscinosis type 8 comprise mixed combinations of granular, curvilinear, and fingerprint profiles.
Q9UBY8	Defects in CLN8 are the cause of neuronal ceroid lipofuscinosis type 8 Northern epilepsy variant (CLN8NE) [MIM:610003]. A form of neuronal ceroid lipofuscinosis clinically characterized by epilepsy that presents between 5 and 10 years of age with frequent tonic-clonic seizures followed by progressive mental retardation. Visual loss is not a prominent feature. Intracellular accumulation of autofluorescent material results in curvilinear and granular profiles on ultrastructural analysis.
Q9QUK3	Defects in Cln8 are the cause of the phenotype motor neuron degeneration (mnd). Mnd is a naturally occurring mutant It is characterized by progressive motor system degeneration. It has intracellular autofluorescent inclusions similar to those seen in human Cln8.
P58418	Defects in CLRN1 are the cause of Usher syndrome type 3 (USH3) [MIM:276902]. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa and sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual progressive deafness and onset of retinitis pigmentosa in the second decade of life.
Q9UJS0	Defects in SLC25A13 are the cause of citrullinemia type 2 (CTLN2) [MIM:603471]. Citrullinemia belongs to the urea cycle disorders. It is an autosomal recessive disease characterized primarily by elevated serum and urine citrulline levels. Ammonia intoxication is another manifestation. CTLN2 is characterized by neuropsychiatric symptoms including abnormal behaviors, loss of memory, seizures and coma. Death can result from brain edema. Onset is sudden and usually between the ages of 20 and 50 years.
Q9UJS0	Defects in SLC25A13 are the cause of neonatal intrahepatic cholestasis due to citrin deficiency (NICCD) [MIM:605814]. NICCD is a form of citrullinemia type 2 with neonatal onset. NICCD is characterized by suppression of the bile flow, hepatic fibrosis, low birth weight, growth retardation, hypoproteinemia, variable liver dysfunction. NICCD is generally not severe and symptoms disappear by one year of age with an appropriate diet. Years or even decades later, however, some individuals develop the characteristic features of citrullinemia type 2 with neuropsychiatric symptoms.
P62633	Defects in CNBP are the cause of myotonic dystrophy 2 (DM2) [MIM:602668]; also known as proximal myotonic myopathy (PROMM). DM2 is an autosomal dominant neurodegenerative disorder characterized by myotonia. DM2 is caused by a CCTG expansion (mean approximately 5000 repeats) located in intron 1 of the CNBP gene.
Q13956	Defects in PDE6H are the cause of cone dystrophy retinal type 3A (RCD3A) [MIM:610024]; also known as cone dystrophy with night blindness and supernormal rod responses. RCD3A is a rare form of cone dystrophy associated with supernormal rod responses. The disorder is characterized by reduced visual acuity, photoaversion, night blindness, and abnormal color vision. At an early age, the retina shows subtle depigmentation at the macula and, later, more obvious areas of atrophy.
Q8BSP2	Defects in Ncaph2 are the cause of the nessy phenotype which is characterized by a specific defect in T-cell development. Nessy thymuses are smaller, with corticomedullary junctions less well defined, and cortical cells sparser than in wild-type. The thymocyte defect is typified by an increased proportion of CD4- CD8- DN T cell progenitors. Only thymocyte differentiation is affected in Nessy mice and not cell differentiation.
P29973	Defects in CNGA1 are a cause of retinitis pigmentosa autosomal recessive (ARRP) [MIM:268000]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
Q16281	Defects in CNGA3 are the cause of achromatopsia type 2 (ACHM2) [MIM:216900]; also known as total colorblindness or rod monochromacy (RMCH2). ACHM2 is an autosomal recessive condition characterized by day blindness and photophobia. In ACHM2 patients the cones are defective and the subjects see better at night.
Q14028	Defects in CNGB1 are the cause of retinitis pigmentosa type 45 (RP45) [MIM:600724]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
Q8MJD7	Defects in CNGB3 are a cause of cone degeneration (cd). Cd is characterized by day-blindness and absence of retinal cone function. This autosomal recessive disorder occurs naturally in the Alaskan Malamute and German Shorthaired Pointer breeds.
Q9NQW8	Defects in CNGB3 are the cause of Stargardt disease type 1 (STGD1) [MIM:248200]. STGD is one of the most frequent causes of macular degeneration in childhood. It is characterized by macular dystrophy with juvenile-onset, rapidly progressive course, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material. STGD1 inheritance is autosomal recessive.
Q9NQW8	Defects in CNGB3 are the cause of achromatopsia type 3 (ACHM3) [MIM:262300]; also known as Pingelapese blindness. ACHM3 is a congenital complete achromatopsia and is distinct from total colorblindness mainly because of the consistent concurrence of severe myopia.
Q6P4Q7	Defects in CNNM4 are the cause of Jalili syndrome (JALIS) [MIM:217080]. A syndrome characterized by the association of cone- rod dystrophy and amelogenesis imperfecta.
Q8VED2	Defects in Cno are the cause of the cappuccino (Cno) mutant, which is characterized by a severe oculocutaneous albinism due to abnormal melanosome formation, and prolonged bleeding due to deficiency of platelet dense body contents.
P09174	Deficiency in GMP-PDE activity cause accumulation of cGMP in visual cells. The elevated cGMP levels are associated with degeneration of the photoreceptors and blindness.
Q12860	Defects in CNTN1 are the cause of Compton-North congenital myopathy [MIM:612540]. Compton-North congenital myopathy is a familial lethal form of congenital onset muscle weakness, inherited in an autosomal-recessive fashion and characterized by a secondary loss of beta2-syntrophin and alpha- dystrobrevin from the muscle sarcolemma, central nervous system involvement, and fetal akinesia.
Q8IWV2	A chromosomal aberration involving CNTN4 has been found in a boy with characteristic physical features of 3p deletion syndrome (3PDS). Translocation t(3;10)(p26;q26). 3PDS is a rare contiguous gene disorder involving the loss of the telomeric portion of the short arm of chromosome 3 and characterized by developmental delay, growth retardation, and dysmorphic features.
Q9UHC6	Defects in CNTNAP2 are the cause of cortical dysplasia- focal epilepsy syndrome (CDFES) [MIM:610042]. Affected individuals manifest cortical dysplasia, focal epilepsy, relative macrocephaly, and diminished deep-tendon reflexes. Intractable focal seizures begin in early childhood, after which language regression, hyperactivity, impulsive and aggressive behavior, and mental retardation develop.
Q9UHC6	Genetic variations in CNTNAP2 influences susceptibility to autism type 15 (AUTS15) [MIM:612100]. Autism is a neurodevelopmental disorder characterized by disturbance in language, perception and socialization. The disorder is classically defined by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypical, and ritualized patterns of interests and behavior.
Q9UHC6	A chromosomal aberration involving CNTNAP2 is found in a patient with autism spectrum disorder. Paracentric inversion 46,XY,inv(7)(q11.22;q35). The inversion breakpoints disrupt the genes AUTS2 and CNTNAP2.
Q9XSJ7	Defects in COL1A1 are a cause of osteogenesis imperfecta (OI).
Q9UML6	Defects in COL1A1 are the cause of Caffey disease [MIM:114000]; also known as infantile cortical hyperostosis. Caffey disease is characterized by an infantile episode of massive subperiosteal new bone formation that typically involves the diaphyses of the long bones, mandible, and clavicles. The involved bones may also appear inflamed, with painful swelling and systemic fever often accompanying the illness. The bone changes usually begin before 5 months of age and resolve before 2 years of age.
Q9UML6	Defects in COL1A1 are a cause of Ehlers-Danlos syndrome type 1 (EDS1) [MIM:130000]; also known as Ehlers-Danlos syndrome gravis. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS1 is the severe form of classic Ehlers-Danlos syndrome.
Q9UML6	Defects in COL1A1 are the cause of Ehlers-Danlos syndrome type 7A (EDS7A) [MIM:130060]; also known as autosomal dominant Ehlers-Danlos syndrome type VII. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS7A is marked by bilateral congenital hip dislocation, hyperlaxity of the joints, and recurrent partial dislocations.
Q9UML6	Defects in COL1A1 are a cause of osteogenesis imperfecta type I (OI-I) [MIM:166200]. OI-I is a dominantly inherited serious newborn disease characterized by bone fragility, normal stature, little or no deformity, blue sclerae and hearing loss in 50% of families. Dentinogenesis imperfecta is rare and may distinguish a subset of OI type I (formation of dentine).
Q9UML6	Defects in COL1A1 are a cause of osteogenesis imperfecta type II (OI-II) [MIM:166210]; also known as osteogenesis imperfecta congenita. OI-II is lethal in the perinatal period and is charaterized by calvarial mineralization, beaded ribs, compressed femurs, marked long bone deformity and platyspondyly (congenital flattening of the vertebral bodies).
Q9UML6	Defects in COL1A1 are a cause of osteogenesis imperfecta type III (OI-III) [MIM:259420]; also known as progressively deforming osteogenesis imperfecta with normal sclerae. OI-III is characterized by progressively deforming bones, usually with moderate deformity at birth, sclerae is variable in color, dentinogenesis imperfecta and hearing loss are common. The stature is very short.
Q9UML6	Defects in COL1A1 are a cause of osteogenesis imperfecta type IV (OI-IV) [MIM:166220]. OI-IV is charaterized by normal sclerae, moderate to mild deformity and variable short stature. Dentinogenesis imperfecta is common and hearing loss occurs in some patients.
Q9UML6	Genetic variations in COL1A1 are associated with susceptibility to involutional osteoporosis [MIM:166710]; also known as senile osteoporosis or postmenopausal osteoporosis. Osteoporosis is characterized by reduced bone mineral density, disrutption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.
Q9UML6	A chromosomal aberration involving COL1A1 is a cause of dermatofibrosarcoma protuberans (DFSP) [MIM:607907]. Translocation t(17;22)(q22;q13) with PDGF. DFSP is an uncommon, locally aggressive, but rarely metastasizing tumor of the deep dermis and subcutaneous tissue. It typically occurs during early or middle adult life and is most frequently located on the trunk and proximal extremities.
Q9UML5	Defects in COL1A2 are the cause of Ehlers-Danlos syndrome type 7B (EDS7B) [MIM:130060]. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS7B is marked by bilateral congenital hip dislocation, hyperlaxity of the joints, and recurrent partial dislocations.
Q9UML5	Defects in COL1A2 are a cause of osteogenesis imperfecta type I (OI-I) [MIM:166200]. OI-I is a dominantly inherited serious newborn disease characterized by bone fragility, normal stature, little or no deformity, blue sclerae and hearing loss in 50% of families. Dentinogenesis imperfecta is rare and may distinguish a subset of OI type I (formation of dentine).
Q9UML5	Defects in COL1A2 are a cause of osteogenesis imperfecta type II (OI-II) [MIM:166210]; also known as osteogenesis imperfecta congenita (OIC) or lethal perinatal. OI-II is a serious newborn disease that diffusely affects bone. Infants are born with multiple fractures, which lead to shortening of the extremities. The skull is soft, and resembles a 'bag of bones' when palpated, the sclera are abnormally thin and may appear blue, and some infants also have a hearing loss. Infants born alive often die suddenly during the first few days or weeks of life, but a few survive as deformed dwarfs. Mental development is normal unless head trauma with CNS injury occurs. There is no effective treatment.
Q9UML5	Defects in COL1A2 are the cause of cardiac valvular form of autosomal recessive Ehlers-Danlos syndrome (cardiac valvular EDS) [MIM:225320]; also known as arthrochalasis type Ehlers-Danlos syndrome. In addition to joint laxity, skin hyperextensibility and friability, and abnormal scar formation, individuals with this form of EDS appear to be at increased risk for cardiac valvular dysfunction.
Q9UML5	Defects in COL1A2 are a cause of osteogenesis imperfecta type III (OI-III) [MIM:259420]. OI-III usually presents with moderate deformity at birth, progressively deforming bones, and sclerae variable in color. Dentinogenesis imperfecta and hearing loss are common. Stature is very short.
Q9UML5	Defects in COL1A2 are a cause of osteogenesis imperfecta type IV (OI-IV) [MIM:166220]; also known as osteogenesis imperfecta with normal sclerae. OI-IV presents with moderate to mild deformity and variable short stature. Dentinogenesis imperfecta is common and hearing loss occurs in some.
Q9UML5	A chromosomal aberration involving COL1A2 may be a cause of lipoblastomas, which are benign tumors resulting from transformation of adipocytes, usually diagnosed in children. Translocation t(7;8)(p22;q13) with PLAG1.
Q96IT5	Defects in COL2A1 are the cause of spondyloepiphyseal dysplasia congenital type (SEDC) [MIM:183900]. This disorder is characterized by disproportionate short stature and pleiotropic involvement of the skeletal and ocular systems.
Q96IT5	Defects in COL2A1 are the cause of Strudwick type spondyloepimetaphyseal dysplasia (SEMD) [MIM:184250]. SEMD is characterized by disproportionate short stature, pectus carinatum, and scoliosis, as well as dappled metaphyses (which is not seen in SEDC).
Q96IT5	Defects in COL2A1 are the cause of achondrogenesis type 2 (ACG2) [MIM:200610]; also known as achondrogenesis- hypochondrogenesis type II. ACG2 is a disease characterized by the absence of ossification in the vertebral column, sacrum and pubic bones.
Q96IT5	Defects in COL2A1 are the cause of Legg-Calve-Perthes disease (LCPD) [MIM:150600]; also known as Legg-Perthes disease or Perthes disease. LCPD is characterized by loss of circulation to the femoral head, resulting in avascular necrosis in a growing child. Clinical pictures of the disease vary, depending on the phase of disease progression through ischemia, revascularization, fracture and collapse, and repair and remodeling of the bone.
Q96IT5	Defects in COL2A1 are the cause of Kniest syndrome (KS) [MIM:156550]; also known as Kniest dysplasia or metatropic dwarfism type II. KS is a moderately severe chondrodysplasia phenotype that results from mutations in the COL2A1 gene. Characteristics of the disorder include a short trunk and extremities, mid-face hypoplasia, cleft palate, myopia, retinal detachment, and hearing loss.
Q96IT5	Defects in COL2A1 are a cause of primary avascular necrosis of femoral head (ANFH) [MIM:608805]; also known as ischemic necrosis of the femoral head or osteonecrosis of the femoral head. ANFH causes disability that often requires surgical intervention. Most cases are sporadic, but families in which there is an autosomal dominant inheritance of the disease have been identified. It has been estimated that 300,000 to 600,000 people in the United States have ANFH. Approximately 15,000 new cases of this common and disabling disorder are reported annually. The age at the onset is earlier than that for osteoarthritis. The diagnosis is typically made when patients are between the ages of 30 and 60 years. The clinical manifestations, such as pain on exertion, a limping gait, and a discrepancy in leg length, cause considerable disability. Moreover, nearly 10 percent of the 500,000 total-hip arthroplasties performed each year in the United States involve patients with ANFH. As a result, this disease creates a substantial socioeconomic cost as well as a burden for patients and their families.
Q96IT5	Defects in COL2A1 are the cause of osteoarthritis with mild chondrodysplasia [MIM:604864]. Osteoarthritis is a common disease that produces joint pain and stiffness together with radiologic evidence of progressive degeneration of joint cartilage. Some forms of osteoarthritis are secondary to events such as trauma, infections, metabolic disorders, or congenital or heritable conditions that deform the epiphyses or related structures. In most patients, however, there is no readily identifiable cause of osteoarthritis. Inheritance in a Mendelian dominant manner has been demonstrated in some families with primary generalized osteoarthritis. Reports demonstrate coinheritance of primary generalized osteoarthritis with specific alleles of the gene COL2A1, the precursor of the major protein of cartilage.
Q96IT5	Defects in COL2A1 are the cause of platyspondylic lethal skeletal dysplasia Torrance type (PLSD-T) [MIM:151210]. Platyspondylic lethal skeletal dysplasias (PLSDs) are a heterogeneous group of chondrodysplasias characterized by severe platyspondyly and limb shortening. PLSD-T is characterized by varying platyspondyly, short ribs with anterior cupping, hypoplasia of the lower ilia with broad ischial and pubic bones, and shortening of the tubular bones with splayed and cupped metaphyses. Histology of the growth plate typically shows focal hypercellularity with slightly enlarged chondrocytes in the resting cartilage and relatively well-preserved columnar formation and ossification at the chondro-osseous junction. PLSD-T is generally a perinatally lethal disease, but a few long-term survivors have been reported.
Q96IT5	Defects in COL2A1 are the cause of multiple epiphyseal dysplasia with myopia and conductive deafness (EDMMD) [MIM:132450]. Multiple epiphyseal dysplasia is a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. EDMMD is an autosomal dominant disorder characterized by epiphyseal dysplasia associated with progressive myopia, retinal thinning, crenated cataracts, conductive deafness.
Q96IT5	Defects in COL2A1 are the cause of spondyloperipheral dysplasia (SPD) [MIM:271700]. SPD patients manifest short stature, midface hypoplasia, sensorineural hearing loss, spondyloepiphyseal dysplasia, platyspondyly and brachydactyly.
Q96IT5	Defects in COL2A1 are the cause of Wagner syndrome type 2 (WGN2). WGN2 is characterized by early-onset cataracts, lattice degeneration of the retina, and retinal detachment without involvement of monocular tissues.
Q96IT5	Defects in COL2A1 are the cause of Stickler syndrome type 1 (STL1) [MIM:108300]; also known as vitreous type 1, or membranous vitreous type. STL1 is an autosomal dominant form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. Ocular disorders may include juvenile cataract, myopia, strabismus, vitreoretinal or chorioretinal degeneration, retinal detachment, and chronic uveitis. Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondylisis and large, often defective epiphyses. Juvenile joint laxity is followed by early signs of arthrosis. The degree of hearing loss varies among affected individuals and may become more severe over time. Syndrome expressivity is variable.
Q96IT5	Defects in COL2A1 are the cause of Stickler syndrome type 1 non-syndromic ocular (STL1O) [MIM:609508]. STL1O is an autosomal dominant form of Stickler syndrome characterized by the ocular signs typically seen in STL1 such as cataract, myopia, retinal detachment. STL1 systemic features of premature osteoarthritis, cleft palate, hearing impairment, and craniofacial abnormalities are either absent or very mild in STL1O patients.
Q96IT5	Defects in COL2A1 are a cause of rhegmatogenous retinal detachment autosomal dominant (DRRD) [MIM:609508]. Rhegmatogenous retinal detachment most frequently results from a break or tear in the retina that allows fluid from the vitreous humor to enter the potential space beneath the retina. It is often associated with pathologic myopia and in most cases leads to visual impairment or blindness if untreated.
Q6LDI9	Defects in Col2a1 are the cause of a phenotype resembling human spondyloepiphyseal dysplasia congenita (sedc). Homozygous sedc mice can be identified at birth by their small size and shortened trunk. Adults have shortened noses, dysplastic vertebrae, femora and tibias, and retinoschisis and hearing loss.
P06681	Defects in C2 are the cause of C2 deficiency (CD2D) [MIM:217000]. CD2D is an autosomal recessive disease. Deficient individuals have an increased incidence of SLE and SLE-like syndromes, glomerulonephritis, vasculitis and pyogenic infections. Type I C2D is characterized by complete loss of the protein while type II C2D is characterized by a selective block in C2 secretion.
Q6LDJ3	Defects in COL3A1 are a cause of Ehlers-Danlos syndrome type 3 (EDS3) [MIM:130020]; also known as benign hypermobility syndrome. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS3 is a form of Ehlers-Danlos syndrome characterized by marked joint hyperextensibility without skeletal deformity.
Q6LDJ3	Defects in COL3A1 are the cause of Ehlers-Danlos syndrome type 4 (EDS4) [MIM:130050]. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS4 is the most severe form of the disease. It is characterized by the joint and dermal manifestations as in other forms of the syndrome, characteristic facial features (acrogeria) in most patients, and by proneness to spontaneous rupture of bowel and large arteries. The vascular complications may affect all anatomical areas.
Q6LDJ3	Defects in COL3A1 are a cause of susceptibility to aortic aneurysm abdominal (AAA) [MIM:100070]. AAA is a common multifactorial disorder characterized by permanent dilation of the abdominal aorta, usually due to degenerative changes in the aortic wall. Histologically, AAA is characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells.
P01024	Defects in C3 are the cause of C3 deficiency [MIM:120700]. It can result in susceptibility to pyogenic infection.
P01024	Genetic variation in C3 is associated with susceptibility to age-related macular degeneration type 9 (ARMD9) [MIM:611378]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
P02462	Defects in COL4A1 are a cause of brain small vessel disease with hemorrhage [MIM:607595]. Brain small vessel diseases underlie 20 to 30 percent of ischemic strokes and a larger proportion of intracerebral hemorrhages. Inheritance is autosomal dominant.
P02462	Defects in COL4A1 are the cause of hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) [MIM:611773]. The clinical renal manifestations include hematuria and bilateral large cysts. Histologic analysis revealed complex basement membrane defects in kidney and skin. The systemic angiopathy appears to affect both small vessels and large arteries.
P02462	Defects in COL4A1 are a cause of porencephaly type 1 [MIM:175780]; also known as encephaloclastic porencephaly. Porencephaly is a term used for any cavitation or cerebrospinal fluid-filled cyst in the brain. Porencephaly type 1 is usually unilateral and results from focal destructive lesions such as fetal vascular occlusion or birth trauma. Inheritance is autosomal dominant.
Q01955	Autoantibodies against the NC1 domain of alpha 3(IV) are found in Goodpasture syndrome, an autoimmune disease of lung and kidney.
Q01955	Defects in COL4A3 are a cause of Alport syndrome autosomal recessive (APSAR) [MIM:203780]. APSAR is characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness.
Q01955	Defects in COL4A3 are a cause of benign familial hematuria (BFH) [MIM:141200]; also known as thin basement membrane nephropathy. BFH is characterized by persistent hematuria, an electron microscopically detectable thin glomerular basement membrane (GBM) and an autosomal dominant mode of inheritance. Renal function remains normal. In children, differentiation between BFH and AS can be difficult, because both disorders are manifested by persistent hematuria and thin GBM at that age.
P53420	Defects in COL4A4 are a cause of Alport syndrome autosomal recessive (APSAR) [MIM:203780]. APSAR is characterized by progressive glomerulonephritis, glomerular basement membrane defects, renal failure, sensorineural deafness and specific eye abnormalities (lenticonous and macular flecks). The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness.
P53420	Defects in COL4A4 are a cause of benign familial hematuria (BFH) [MIM:141200]; also known as thin basement membrane nephropathy. BFH is characterized by persistent hematuria, an electron microscopically detectable thin glomerular basement membrane (GBM) and an autosomal dominant mode of inheritance. Renal function remains normal. In children, differentiation between BFH and AS can be difficult, because both disorders are manifested by persistent hematuria and thin GBM at that age.
Q28247	A defect in COL4A5 has been found to be the cause of canine X-linked hereditary nephritis (HN), a disease similar to that in humans (also referred to as Alport syndrome) characterized by progressive renal failure and neurosensory deafness.
P29400	Defects in COL4A5 are the cause of Alport syndrome X- linked (APSX) [MIM:301050]. APSX is characterized by progressive glomerulonephritis, renal failure, sensorineural deafness, specific eye abnormalities (lenticonous and macular flecks), and glomerular basement membrane defects. The disorder shows considerable heterogeneity in that families differ in the age of end-stage renal disease and the occurrence of deafness.
P29400	Deletions covering the N-terminal regions of COL4A5 and COL4A6, which are localized in a head-to-head manner, are the cause of diffuse leiomyomatosis with Alport syndrome (DL-ATS) [MIM:308940]; also known as esophageal and vulval leiomyomatosis with nephropathy or Alport syndrome and diffuse leiomyomatosis (ATS-DL). DL-ATS is the combination of AS and diffuse leiomyomatosis (DL). DL is a tumorous process involving smooth muscle cells, mostly of the esophagus, but also of the tracheobronchial tree and the female genital tract.
Q9UMG6	Deletions covering the N-terminal regions of COL4A6 and COL4A5, which are localized in a head-to-head manner, are the cause of diffuse leiomyomatosis with Alport syndrome (DL-ATS) [MIM:308940]; also known as esophageal and vulval leiomyomatosis with nephropathy or Alport syndrome and diffuse leiomyomatosis (ATS-DL). DL-ATS is the combination of Alport syndrome (AS) and diffuse leiomyomatosis (DL). AS is characterized by progressive glomerulonephritis, often associated with high-tone sensorineural deafness, specific eye abnormalities (lenticonous and macular flecks), and glomerular basement membrane defects. DL is a tumorous process involving smooth muscle cells, mostly of the esophagus, but also of the tracheobronchial tree and the female genital tract.
Q5JQM8	Defects in C4A are the cause of C4A deficiency [MIM:120810].
P20908	Defects in COL5A1 are a cause of Ehlers-Danlos syndrome type 1 (EDS1) [MIM:130000]; also known as Ehlers-Danlos syndrome gravis or severe classic type Ehlers-Danlos syndrome. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS1 is the severe form of classic Ehlers-Danlos syndrome.
P20908	Defects in COL5A1 are a cause of Ehlers-Danlos syndrome type 2 (EDS2) [MIM:130010]; also known as Ehlers-Danlos syndrome mitis or mild classic type Ehlers Danlos syndrome.
Q96QB0	Defects in COL5A2 are a cause of Ehlers-Danlos syndrome type 1 (EDS1) [MIM:130000]; also known as Ehlers-Danlos syndrome gravis or severe classic type Ehlers-Danlos syndrome. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS1 is the severe form of classic Ehlers-Danlos syndrome.
Q96QB0	Defects in COL5A2 are a cause of Ehlers-Danlos syndrome type 2 (EDS2) [MIM:130010]; also known as Ehlers-Danlos syndrome mitis or mild classic type Ehlers Danlos syndrome.
P01031	Defects in C5 are the cause of complement C5 deficiency [MIM:609536]. Patients with dysfunction of C5 display a propensity for severe recurrent infections.
P01031	Genetic variation in C5 can be associated with susceptibility to liver fibrosis [MIM:120900]. Liver fibrosis is a common consequence of all chronic liver diseases, irrespective of etiology. Common C5 variants can influence the progression and severity of fibrogenesis.
P12109	Defects in COL6A1 are a cause of Bethlem myopathy (BM) [MIM:158810]. BM is a rare autosomal dominant proximal myopathy characterized by early childhood onset (complete penetrance by the age of 5) and joint contractures most frequently affecting the elbows and ankles.
P12109	Defects in COL6A1 are a cause of Ullrich congenital muscular dystrophy (UCMD) [MIM:254090]; also known as Ullrich scleroatonic muscular dystrophy. UCMD is an autosomal recessive congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy.
Q6P0Q1	Defects in COL6A2 are a cause of Bethlem myopathy (BM) [MIM:158810]. BM is a rare autosomal dominant proximal myopathy characterized by early childhood onset (complete penetrance by the age of 5) and joint contractures most frequently affecting the elbows and ankles.
Q6P0Q1	Defects in COL6A2 are a cause of Ullrich congenital muscular dystrophy (UCMD) [MIM:254090]; also known as Ullrich scleroatonic muscular dystrophy. UCMD is an autosomal recessive congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy.
Q6P0Q1	Defects in COL6A2 are the cause of autosomal recessive myosclerosis [MIM:255600]; also known as myosclerotic myopathy or congenital myosclerosis of Lowenthal. Myosclerosis consists of a chronic inflammation of skeletal muscle with hyperplasia of the interstitial connective tissue. It is first considered a new familial degenerative illness of the intermysial connective tissue in a report of patients in families presenting a restriction of articular mobility. Difficulty in walking is noted in early childhood, together with toe walking and progressive calf contractures. The clinical picture is characterized by slender muscles with firm 'woody' consistency and restriction of movement of many joints because of muscle contractures.
P12111	Defects in COL6A3 are a cause of Bethlem myopathy (BM) [MIM:158810]. BM is a rare autosomal dominant proximal myopathy characterized by early childhood onset (complete penetrance by the age of 5) and joint contractures most frequently affecting the elbows and ankles.
P12111	Defects in COL6A3 are a cause of Ullrich congenital muscular dystrophy (UCMD) [MIM:254090]; also known as Ullrich scleroatonic muscular dystrophy. UCMD is an autosomal recessive congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy.
B5MEA7	Genetic variation of COL29A1 may be associated with susceptibility to atopic dermatitis (ATOD) [MIM:603165]. ATOP, also known as eczema commonly begins in infancy or early childhook and is characterized by itchy and inflamed skin.
P13671	Defects in C6 are the cause of complement component 6 deficiency (C6D) [MIM:612446].
Q02388	Epidermolysis bullosa acquisita (EBA) is an autoimmune acquired blistering skin disease resulting from autoantibodies to type VII collagen.
Q02388	Defects in COL7A1 are the cause of epidermolysis bullosa dystrophica (DEB) [MIM:131750, 226600]. DEB defines a group of blistering skin diseases characterized by tissue separation which occurs below the dermal-epidermal basement membrane at the level of the anchoring fibrils. Inheritance can be autosomal dominant or recessive. Various clinical types with different severity are recognized, ranging from severe mutilating forms to mild forms with limited and localized scarring, and less frequent extracutaneous manifestations. Mild forms include epidermolysis bullosa mitis and epidermolysis bullosa localisata.
Q02388	Defects in COL7A1 are the cause of epidermolysis bullosa dystrophica Pasini type (P-DEB) [MIM:131750]; also known as albopapuloid dominant dystrophic epidermolysis bullosa. P-DEB is a severe, dominantly inherited form of dystrophic epidermolysis bullosa characterized by albopapuloid Pasini papule, dorsal extremity blistering, milia formation and red atrophic scarring after recurrent blisters.
Q02388	Defects in COL7A1 are the cause of epidermolysis bullosa dystrophica Hallopeau-Siemens type (HS-DEB) [MIM:226600]. HS-DEB is the most severe recessive form and manifests with mutilating scarring, joint contractures, corneal erosions, esophagus structures, and propensity to formation of cutaneous squamous cell carcinomas leading to premature demise of the affected individuals.
Q02388	Defects in COL7A1 are the cause of transient bullous dermolysis of the newborn (TBDN) [MIM:131705]. TBDN is a neonatal form of dystrophic epidermolysis bullosa characterized by sub- epidermal blisters, reduced or abnormal anchoring fibrils at the dermo-epidermal junction, and electron-dense inclusions in keratinocytes. TBDN heals spontaneously or strongly improves within the first months and years of life.
Q02388	Defects in COL7A1 are the cause of epidermolysis bullosa dystrophica pretibial type (PR-DEB) [MIM:131850]. PR-DEB is characterized by pretibial blisters that develop into prurigo-like hyperkeratotic lesions. It predominantly affects the pretibial areas, sparing the knees and other parts of the skin. Other clinical features include nail dystrophy, albopapuloid skin lesions, and hypertrophic scars without pretibial predominance. The phenotype shows considerable interindividual variability Inheritance is autosomal dominant.
Q02388	Defects in COL7A1 are the cause of epidermolysis bullosa dystrophica Bart type (B-DEB) [MIM:132000]. B-DEB is an autosomal dominant form of dystrophic epidermolysis bullosa characterized by congenital localized absence of skin, skin fragility and deformity of nails.
Q02388	Defects in COL7A1 are the cause of epidermolysis bullosa pruriginosa (EBP) [MIM:604129]. EBP is a distinct clinical subtype of DEB. It is characterized by skin fragility, blistering, scar formation, intense pruritus and excoriated prurigo nodules. Onset is in early childhood, but in some cases is delayed until the second or third decade of life. Inheritance can be autosomal dominant or recessive.
Q02388	Defects in COL7A1 are the cause of isolated toenail dystrophy without skin fragility [MIM:607523].
Q02388	Defects in COL7A1 are the cause of epidermolysis bullosa dystrophica with subcorneal cleavage (EBDSC) [MIM:607600]; also known as epidermolysis bullosa simplex superficialis (EBSS). EBDSC is a new variant of epidermolysis bullosa simplex (EBS), characterized by the development of skin cleavage just beneath the level of stratum corneum. It appears to be transmitted as an autosomal dominant trait and differs from other autosomal dominant forms of EBS by the common findings of milia and atrophic scarring, as well as involvement of oral and/or ocular surfaces. It is further differentiated by the presence of blisters and the absence of spontaneous continual exfoliation or peeling.
P10643	Defects in C7 are a cause of component C7 deficiency (C7D) [MIM:217070]. Patients with C7D suffer from recurrent bacterial infections, predominantly from Neisseria meningitidis.
P25067	Defects in COL8A2 are a cause of posterior polymorphous corneal dystrophy (PPCD) [MIM:122000]. PPCD is a slowly progressive hereditary disorder of the corneal endothelium that leads to a variable degree of visual impairment usually in adulthood. PPCD is usually inherited as an autosomal dominant trait.
P25067	Defects in COL8A2 are a cause of Fuchs endothelial corneal dystrophy (FECD) [MIM:136800]. FECD is the commonest primary disorder of the corneal endothelium in developed countries. Symptoms of painful visual loss result from corneal decompensation. Signs may be present from the fourth decade of life onwards. Tipically, focal wart-like guttata arising from Descemet membrane develops in the central cornea; Descemet membrane is thickened by abnormal collagenous deposition. FECD is usually sporadic but familial highly penetrant forms showing autosomal dominant inheritance are also recognized.
P25067	Defects in COL8A2 are the cause of posterior polymorphous corneal dystrophy type 2 (PPCD2) [MIM:609140]. PPCD is a rare bilateral familial disorder of the corneal epithelium, and is inherited in a autosomal dominant pattern. The clinical features usually present earlier than FECD, being from birth onwards. The disorder is characterized by alterations of Descemet membrane presenting as vesicles, opacities or band-like lesions on slit- lamp examination and specular microscopy. Affected patient typically are asymptomatic.
P07357	Defects in C8A are a cause of complement C8 deficiency type I [MIM:120950]. Patients with deficiency of C8 suffer from recurrent bacterial infections, predominantly from Neisseria meningitidis.
P07358	Defects in C8B are a cause of complement C8 deficiency type II [MIM:120960]. Patients with deficiency of C8 suffer from recurrent bacterial infections, predominantly from Neisseria meningitidis.
Q9H152	Defects in COL9A1 are a cause of COL9A1-related multiple epiphyseal dysplasia (COL9A1-MED) [MIM:120210].
Q9H152	Defects in COL9A1 are the cause of Stickler syndrome autosomal recessive COL9A1-related (COL9A1ARSTL) [MIM:120210]. COL9A1ARSTL is an autosomal recessive form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. Ocular disorders may include juvenile cataract, myopia, strabismus, vitreoretinal or chorioretinal degeneration, retinal detachment, and chronic uveitis. Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondylisis and large, often defective epiphyses. Juvenile joint laxity is followed by early signs of arthrosis. The degree of hearing loss varies among affected individuals and may become more severe over time. Syndrome expressivity is variable.
Q14055	Defects in COL9A2 are the cause of multiple epiphyseal dysplasia type 2 (EDM2) [MIM:600204]. EDM is a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. EDM is broadly categorized into the more severe Fairbank and the milder Ribbing types. EDM2 inheritance is autosomal dominant.
Q14055	Defects in COL9A2 may be a cause of susceptibility to intervertebral disc disease (IDD) [MIM:603932]; also known as lumbar disk herniation (LDH). IDD is one of the most common musculo-skeletal disorders and the predominant cause of low-back pain and unilateral leg pain.
Q14050	Defects in COL9A3 are the cause of multiple epiphyseal dysplasia type 3 (EDM3) [MIM:600969]; also known as multiple epiphyseal dysplasia with myopathy. EDM is a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. EDM is broadly categorized into the more severe Fairbank and the milder Ribbing types.
P02748	Defects in C9 are a cause of component C9 deficiency (C9D) [MIM:120940]. Patients with C9D suffer from recurrent bacterial infections, predominantly from Neisseria meningitidis.
Q03692	Defects in COL10A1 are the cause of Schmid type metaphyseal chondrodysplasia (SMCD) [MIM:156500]. SMCD is a dominantly inherited disorder of the osseous skeleton. The cardinal features of the phenotype are mild short stature, coxa vara and a waddling gait. Radiography usually shows sclerosis of the ribs, flaring of the metaphyses, and a wide irregular growth plate, especially of the knees. A variant form of SMCD is spondylometaphyseal dysplasia Japanese type. It is characterized by spinal involvement comprising mild platyspondyly, vertebral body abnormalities, and end-plate irregularity.
P12107	Defects in COL11A1 are the cause of Stickler syndrome type 2 (STL2) [MIM:604841]; also known as Stickler syndrome vitreous type 2. STL2 is an autosomal dominant form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. Ocular disorders may include juvenile cataract, myopia, strabismus, vitreoretinal or chorioretinal degeneration, retinal detachment, and chronic uveitis. Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondylisis and large, often defective epiphyses. Juvenile joint laxity is followed by early signs of arthrosis. The degree of hearing loss varies among affected individuals and may become more severe over time. Syndrome expressivity is variable.
P12107	Defects in COL11A1 are the cause of Marshall syndrome [MIM:154780]. It is an autosomal dominant disorder with ocular, orofacial, auditory and skeletal manifestations. It shares several features with Stickler syndrome, such as midfacial hypoplasia, high myopia, and sensorineural-hearing deficit.
Q61245	Defects in Col11a1 are associated with chondrodysplasia, an autosomal recessive disease characterized by skeletal defects caused by abnormalities in the cartilage of limbs, ribs, mandibles and trachea.
Q9UIP9	Defects in COL11A2 are the cause of Stickler syndrome type 3 (STL3) [MIM:184840]. STL3 is an autosomal dominant non- ocular form of Stickler syndrome. Classical Stickler syndrome associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. Ocular symptoms are absent in STL3. Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondylisis and large, often defective epiphyses. Juvenile joint laxity is followed by early signs of arthrosis. The degree of hearing loss varies among affected individuals and may become more severe over time. Syndrome expressivity is variable.
Q9UIP9	Defects in COL11A2 are the cause of autosomal recessive otospondylomegaepiphyseal dysplasia (OSMED) [MIM:215150]. OSMED is a skeletal dysplasia accompanied by severe hearing loss. The phenotype overlaps that of autosomal dominant skeletal disorders (Stickler and Marshall syndromes) but can be distinguished by disproportionately short limbs and lack of ocular involvement.
Q9UIP9	Defects in COL11A2 are the cause of Weissenbacher- Zweymueller syndrome (WZS) [MIM:277610]. WZS is an autosomal dominant disorder allelic with STL3 and OSMED. WZS is also referred to as heterozygous OSMED.
Q9UIP9	Defects in COL11A2 are the cause of non-syndromic sensorineural deafness autosomal dominant type 13 (DFNA13) [MIM:601868]. DFNA13 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Q9UIP9	Defects in COL11A2 are the cause of non-syndromic sensorineural deafness autosomal recessive type 53 (DFNB53) [MIM:609706].
O43405	Defects in COCH are the cause of non-syndromic sensorineural deafness autosomal dominant type 9 (DFNA9) [MIM:601369]. DFNA9 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA9 is characterized by onset in the fourth or fifth decade of life and initially involves the high frequencies. Deafness is progressive and usually complete by the sixth decade. In addition to cochlear involvement, DFNA9 patients also exhibit a spectrum of vestibular dysfunctions. Penetrance of the vestibular symptoms is often incomplete, and some patients are minimally affected, whereas others suffer from severe balance disturbances and episodes of vertigo. Affected individuals have mucopolysaccharide depositions in the channels of the cochlear and vestibular nerves. These depositions apparently cause strangulation and degeneration of dendritic fibers.
O43405	Defects in COCH may contribute to Meniere disease [MIM:156000]. Meniere disease is an autosomal dominant disorder characterized by hearing loss associated with episodic vertigo. Antibodies against COCH are found in 10% of Meniere patients.
Q9Y281	Defects in CFL2 are the cause of nemaline myopathy type 7 (NEM7) [MIM:610687]. A form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-or rod-like structures in muscle fibers on histologic examination. Nemaline myopathy type 7 presents at birth with hypotonia and generalized weakness. Major motor milestones are delayed, but independent ambulation is achieved.
Q8WTW3	Defects in COG1 are the cause of congenital disorder of glycosylation type 2G (CDG2G) [MIM:611209]; also known as CDG-II caused by COG1 deficiency. CDGs are a family of severe inherited diseases caused by a defect in glycoprotein biosynthesis. They are characterized by under-glycosylated serum glycoproteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Clinical features of CDG2G include failure to thrive, generalized hypotonia, growth retardation and mild psychomotor retardation. CDG2G is biochemically characterized by a defect in O-glycosylation as well as N-glycosylation.
P83436	Defects in COG7 are the cause of congenital disorder of glycosylation type 2E (CDG2E) [MIM:608779]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q96MW5	Defects in COG8 are the cause of congenital disorder of glycosylation type 2H (CDG2H) [MIM:611182]. CDGs are a family of severe inherited diseases caused by a defect in protein N- glycosylation. They are characterized by under-glycosylated serum proteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
Q9N281	Defects in COL17A1 are the cause of generalized atrophic benign epidermolysis bullosa. This nonlethal form of junctional epidermolysis bullosa is characterized by life-long blistering of the skin, associated with hair and tooth abnormalities.
Q9UMD9	Defects in COL17A1 are a cause of generalized atrophic benign epidermolysis bullosa (GABEB) [MIM:226650]. GABEB is a non- lethal, adult form of junctional epidermolysis bullosa characterized by life-long blistering of the skin, associated with hair and tooth abnormalities.
Q96T70	Defects in COL18A1 are a cause of Knobloch syndrome (KNO) [MIM:267750]. KNO is an autosomal recessive disorder defined by the occurrence of high myopia, vitreoretinal degeneration with retinal detachment, macular abnormalities and occipital encephalocele.
P01189	Defects in POMC may be associated with susceptibility to obesity [MIM:601665].
P01189	Defects in POMC are the cause of pro-opiomelanocortinin deficiency [MIM:609734]. Affected individuals present early-onset obesity, adrenal insufficiency and red hair.
Q9NP19	Defects in COLQ are the cause of congenital myasthenic syndrome Engel type (CMSE) [MIM:603034]; also known as end-plate acetylcholinesterase deficiency or congenital myasthenic syndrome type IC (CMS-IC). CMSE is a rare autosomal recessive congenital myasthenic syndrome characterized by onset during childhood, generalized weakness, abnormal fatigability on exertion, refrectoriness to acetylcholinesterase drugs, decremental electromyographic response and morphological abnormalities of the neuromuscular junctions.
Q8WMD0	Defects in COMMD1 are the cause of copper toxicosis (CT) in Bedlington terriers, a genetic disease occurring with a high prevalence worldwide and is unique to this breed. In Bedlington terriers the biliary excretion of copper is impaired.
P49747	Defects in COMP are the cause of multiple epiphyseal dysplasia type 1 (EDM1) [MIM:132400]. EDM is a generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. EDM is broadly categorized into the more severe Fairbank and the milder Ribbing types.
P49747	Defects in COMP are the cause of pseudoachondroplasia (PSACH) [MIM:177170]. PSAC is a dominantly inherited chondrodysplasia characterized by short stature and early-onset osteoarthrosis. PSACH is more severe than EDM1 and is recognized in early childhood.
Q96H96	Defects in COQ2 are a cause of coenzyme Q10 deficiency [MIM:607426]. Coenzyme Q10 deficiency is an autosomal recessive disorder with variable manifestations. It can be associated with three main clinical phenotypes: a predominantly myopathic form with central nervous system involvement, an infantile encephalomyopathy with renal dysfunction and an ataxic form with cerebellar atrophy.
Q12887	Defects in COX10 are a cause of cytochrome c oxidase deficiency (COX deficiency) [MIM:220110]. A metabolic disorder with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, excercise intolerance, developmental delay, delayed motor development and mental retardation, lactic acidosis.
Q12887	Defects in COX10 are a cause of Leigh syndrome (LS) [MIM:256000]. LS is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions.
Q7KZN9	Defects in COX15 are a cause of cytochrome c oxidase deficiency (COX deficiency) [MIM:220110]. A metabolic disorder with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, excercise intolerance, developmental delay, delayed motor development and mental retardation, lactic acidosis.
Q7KZN9	Defects in COX15 are a cause of Leigh syndrome [MIM:256000]. Leigh syndrome is an early-onset progressive neurodegenerative disorder characterized by delayed onset of symptoms, hypotonia, feeding difficulties, failure to thrive, motor regression and brainstem signs. Diagnosis is confirmed by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord.
P00395	Defects in MT-CO1 are a cause of Leber hereditary optic neuropathy (LHON) [MIM:535000]. LHON is a maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
P00395	Defects in MT-CO1 are a cause of anemia sideroblastic acquired idiopathic (AISA) [MIM:516030]; a disease characterized by inadequate formation of heme and excessive accumulation of iron in mitochondria.
P00395	Defects in MT-CO1 are a cause of cytochrome c oxidase deficiency (COX deficiency) [MIM:220110]. A metabolic disorder with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, excercise intolerance, developmental delay, delayed motor development and mental retardation, lactic acidosis.
P00395	Defects in MT-CO1 are associated with recurrent myoglobinuria [MIM:550500]. Myoglobinuria consists of excretion of myoglobin in the urine.
P00403	Defects in MT-CO2 are a cause of cytochrome c oxidase deficiency (COX deficiency) [MIM:220110]. A metabolic disorder with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, excercise intolerance, developmental delay, delayed motor development and mental retardation, lactic acidosis.
P00414	Defects in MT-CO3 are a cause of Leber hereditary optic neuropathy (LHON) [MIM:535000]. LHON is a maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
P00414	Defects in MT-CO3 are a cause of cytochrome c oxidase deficiency (COX deficiency) [MIM:220110]. A metabolic disorder with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, excercise intolerance, developmental delay, delayed motor development and mental retardation, lactic acidosis.
P00414	Defects in MT-CO3 are associated with recurrent myoglobinuria [MIM:550500]. Myoglobinuria consists of excretion of myoglobin in the urine.
Q96KJ9	Defects in COX4I2 are the cause of exocrine pancreatic insufficiency dyserythropoietic anemia and calvarial hyperostosis [MIM:612714]. Patients present with pancreatic insufficiency, intestinal malabsorption, failure to thrive, and anemia soon after birth.
Q8TEP3	A chromosomal aberration involving CEP110 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with FGFR1. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CEP110-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.
P05108	Defects in CYP11A1 are a cause of congenital adrenal insufficiency (CAI).
P05108	Defects in CYP11A1 are a cause of congenital lipoid adrenal hyperplasia (CLAH) [MIM:201710]; also known as lipoid CAH. CLAH is the most severe form of adrenal hyperplasia. This autosomal recessive and potentially lethal condition includes the onset of profound adrenocortical insufficiency shortly after birth, hyperpigmentation reflecting increased production of pro- opiomelanocortin, elevated plasma renin activity as a consequence of reduced aldosterone synthesis, and male pseudohermaphroditism resulting from deficient fetal testicular testosterone synthesis. CLAH is a rare disease, except in Japan and Korea where it accounts for a significant percentage of cases of congenital adrenal hyperplasia.
P05093	Defects in CYP17A1 are the cause of adrenal hyperplasia type 5 (AH5) [MIM:202110]. AH5 is a form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: "salt wasting" (SW, the most severe type), "simple virilizing" (SV, less severely affected patients), with normal aldosterone biosynthesis, "non-classic form" or late onset (NC or LOAH), and "cryptic" (asymptomatic).
P11511	Defects in CYP19A1 are a cause of familial gynecomastia [MIM:139300]. This is characterized by an estrogen excess due to an increased aromatase activity.
P11511	Defects in CYP19A1 are the cause of aromatase deficiency (AROD) [MIM:107910]. AROD is a rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female babies present with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries.
Q16678	Defects in CYP1B1 are the cause of primary congenital glaucoma type 3A (GLC3A) [MIM:231300]. GLC3A is an autosomal recessive form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor.
Q16678	Defects in CYP1B1 are a cause of primary open angle glaucoma (POAG) [MIM:137760]. POAG is a complex and genetically heterogeneous ocular disorder characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. The disease is asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. In some cases, POAG shows digenic inheritance involving mutations in CYP1B1 and MYOC genes.
Q16678	Defects in CYP1B1 are a cause of Peters anomaly [MIM:604229]. Peters anomaly is a congenital defect of the anterior chamber of the eye.
P08686	Defects in CYP21A2 are the cause of adrenal hyperplasia type 3 (AH3) [MIM:201910]. AH3 is a form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late onset (NC or LOAH), and 'cryptic' (asymptomatic).
Q02318	Defects in CYP27A1 are the cause of cerebrotendinous xanthomatosis (CTX) [MIM:213700]. CTX is a rare sterol storage disorder characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts.
O15528	Defects in CYP27B1 are a cause of vitamin D-dependent rickets type 1 (VDDR-1) [MIM:264700]; also known as pseudovitamin D deficiency rickets (PDDR). VDDR-1 is an autosomal recessive disease characterized by muscle weakness and early onset of rickets with hypocalcemia.
Q6VVX0	Defects in CYP2R1 are a cause of 25-hydroxyvitamin D(3) deficiency (25HOD3D)[MIM:600081]; also known as pseudovitamin D(3) deficiency rickets due to 25-hydroxylase deficiency. First described in patients who had rickets at a young age despite a history of adequate vitamin D intake. The patients sera had low calcium concentrations, low phosphate concentrations, elevated alkaline phosphatase activity, and low levels of 25-hydroxyvitamin D.
Q6NT55	Defects in CYP4F22 are the cause of ichthyosis lamellar type 3 (LI3) [MIM:604777]. LI is a non-bullous ichthyosis, a skin disorder characterized by abnormal cornification of the epidermis. It is one the most severe forms of ichthyoses apparent at birth and persisting throughout life. LI patients are born encased in a tight, shiny, translucent covering called collodion membrane. Over the first weeks of life, the collodion membrane is gradually replaced by generalized large, dark brown, plate-like scales with minimal to no erythroderma. Tautness of facial skin commonly results in ectropion, eclabium and scarring alopecia of the scalp. Common complications are severe heat intolerance and recurrent ear infections.
Q6ZWL3	Defects in CYP4V2 are a cause of Bietti crystalline corneoretinal dystrophy (BCD) [MIM:210370]. BCD is an autosomal recessive retinal dystrophy characterized by multiple glistening intraretinal crystals scattered over the fundus, a characteristic degeneration of the retina, and sclerosis of the choroidal vessels, ultimately resulting in progressive night blindness and constriction of the visual field. Most cases have similar crystals at the corneoscleral limbus. Clinically, BCD is progressive. Patients develop decreased vision, nyctalopia, and paracentral scotomata between the 2nd and 4th decade of life. Later, patients develop peripheral visual field loss and marked visual impairment, usually progressing to legal blindness by the 5th or 6th decade of life.
O75881	Defects in CYP7B1 are the cause of spastic paraplegia autosomal recessive type 5A (SPG5A) [MIM:270800]. Spastic paraplegia is a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body.
O75881	Defects in CYP7B1 are the cause of congenital bile acid synthesis defect type 3 (CBAS3) [MIM:603711]. Clinical features include severe cholestasis, cirrhosis and liver synthetic failure. Hepatic microsomal oxysterol 7-alpha-hydroxylase activity is undetectable.
P31327	Defects in CPS1 are the cause of carbamoyl phosphate synthetase 1 deficiency (CPS1D) [MIM:237300]. CPS1D is an autosomal recessive disorder of the urea cycle causing hyperammonemia. Clinical features include protein intolerance, intermittent ataxia, seizures, lethargy, developmental delay and mental retardation.
P31327	Defects in CPS1 are associated with susceptibility to familial persistent pulmonary hypertension of the newborn [MIM:265380]; also called congenital alveolar capillary dysplasia or CACD. Failure of the transition to a cardiorespiratory circulation at birth results in persistent pulmonary hypertension of the newborn. Characterized by elevated pulmonary vascular resistance with extrapulmonary right-to-left shunting of blood across the patent ductus arteriosus or the foramen ovale, persistent pulmonary hypertension can cause life-threatening hypoxemia in newborn infants. Transitional pulmonary hypertension occurs in 1.9 of every 1000 newborn infants and is associated with a mortality rate of 11 percent.
P50416	Defects in CPT1A are the cause of carnitine palmitoyltransferase 1A deficiency (CPT1AD) [MIM:255120]; also known as CPT-I deficiency or CPT1A deficiency. CPT1AD is a rare autosomal recessive metabolic disorder of long-chain fatty acid oxidation characterized by severe episodes of hypoketotic hypoglycemia usually occurring after fasting or illness. Onset is in infancy or early childhood.
P23786	Defects in CPT2 are the cause of carnitine palmitoyltransferase 2 deficiency (CPT2D) [MIM:255110, 600649]; also known as CPT-II deficiency or CPT2 deficiency. CPT2D is an autosomal recessive disorder characterized by recurrent myoglobinuria, episodes of muscle pain, stiffness, and rhabdomyolysis. These symptoms are triggered by prolonged exercise, fasting or viral infection and patients are usually young adults. In addition to this classical, late-onset, muscular type, a hepatic or hepatocardiomuscular form has been reported in infants. Clinical pictures in these children or neonates include hypoketotic hypoglycemia, liver dysfunction, cardiomyopathy and sudden death.
P23786	Defects in CPT2 are the cause of carnitine palmitoyltransferase 2 deficiency, lethal neonatal (CPT2D-LN) [MIM:608836]; also known as lethal neonatal CPT-II deficiency. It is a lethal neonatal form of CPT2D. This rarely presentation is antenatal with cerebral periventricular cysts and cystic dysplastic kidneys. The clinical variability of the disease is likely attributed to the variable residual enzymatic activity.
P20023	Genetic variations in CR2 are associated with susceptibility to systemic lupus erythematosus type 9 (SLEB9) [MIM:610927]. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex genetic basis. SLE is an inflammatory, and often febrile multisystemic disorder of connective tissue characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system.
Q70SY1	A chromosomal aberration involving CREB3L2 is found in low grade fibromyxoid sarcoma (LGFMS). Translocation t(7;16)(q33;p11) with FUS.
P05813	Defects in CRYBA1 are the cause of cataract congenital zonular with sutural opacities (CCZS) [MIM:600881]. A form of zonular cataract. Zonular or lamellar cataracts are concentric opacities, broad or narrow, usually consisting of powdery white dots affecting one lamella or zonule of an otherwise clear lens.
P53673	Defects in CRYBA4 are the cause of cataract zonular type 2 (CZ2) [MIM:610425]; also known as lamellar cataract 2. A form of zonular cataract. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes.
P53673	Defects in CRYBA4 are a cause of microphthalmia isolated with cataract type 4 (MCOPCT4) [MIM:610426]. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, cataractand other abnormalities like cataract may also be present.
P53674	Defects in CRYBB1 are the cause of cataract congenital nuclear autosomal recessive type 3 (CATCN3) [MIM:611544]. A congenital cataract affecting the central nucleus of the eye. Nuclear cataracts are often not highly visually significant. The density of the opacities varies greatly from fine dots to a dense, white and chalk-like, central cataract. The condition is usually bilateral. Nuclear cataracts are often combined with opacified cortical fibers encircling the nuclear opacity, which are referred to as cortical riders.
P43320	Defects in CRYBB2 are the cause of cataract congenital cerulean type 2 (CCA2) [MIM:601547]; also known as congenital cataract blue dot type 2. A cerulean form of autosomal dominant congenital cataract. Cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract.
P43320	Defects in CRYBB2 are the cause of cataract sutural with punctate and cerulean opacities (CSPC) [MIM:607133]. A form of cataract characterized by white opacification around the anterior and posterior Y sutures, and grayish and bluish, spindle shaped, oval punctate and cerulean opacities of various sizes arranged in lamellar form. The spots are more concentrated towards the peripheral layers and do not delineate the embryonal or fetal nucleus. Phenotypic variation with respect to the size and density of the sutural opacities as well as the number and position of punctate and cerulean spots is observed among affected subjects.
P43320	Defects in CRYBB2 are a cause of cataract Coppock-like (CCL) [MIM:604307]. A congenital pulverulent disk-like opacity involving the embryonic nucleus with many tiny white dots in the lamellar portion of the lens. It is usually bilateral and dominantly inherited.
P26998	Defects in CRYBB3 are the cause of cataract congenital nuclear autosomal recessive type 2 (CATCN2) [MIM:609741]. A congenital cataract affecting the central nucleus of the eye. Nuclear cataracts are often not highly visually significant. The density of the opacities varies greatly from fine dots to a dense, white and chalk-like, central cataract. The condition is usually bilateral. Nuclear cataracts are often combined with opacified cortical fibers encircling the nuclear opacity, which are referred to as cortical riders.
Q96SW2	Defects in CRBN are the cause of mental retardation autosomal recessive type 2A (MRT2A) [MIM:607417]. MRT2A patients display mild mental retardation with a standard IQ ranged from 50 to 70. IQ scores are lower in males than females. Developmental milestones are mildly delayed. There are no dysmorphic or autistic features. Non-syndromic mental retardation patients do not manifest other clinical signs.
Q96D31	Defects in ORAI1 are a cause of severe combined immunodeficiency with CRAC channel dysfunction (CRAC-SCID) [MIM:610277]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T- cell development.
P16220	A chromosomal aberration involving CREB1 is associated with angiomatoid fibrous histiocytoma (AFH) [MIM:612160]. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type.
Q96HD1	Defects in CRELD1 may be the cause of susceptibility to atrioventricular septal defect type 2 (AVSD2) [MIM:606217, 600309]. AVSD is a spectrum of cardiac malformations that result in a persistent common atrioventricular canal. The complete form of AVSD involves underdevelopment of the lower part of the atrial septum and the upper part of the ventricular septum. A less severe form, known as partial AVSD or ostium primum atrial septal defect has a deficiency of the atrial septum. Complete AVSD are clinically apparent at birth, whereas less severe forms, such as an isolated cleft mitral valve or small defects of the atrial or ventricular septa may go undetected.
P07315	Defects in CRYGC are a cause of cataract autosomal dominant (ADC) [MIM:604219]. Cataract is an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. Cataract is the most common treatable cause of visual disability in childhood.
P07315	Defects in CRYGC are a cause of cataract Coppock-like (CCL) [MIM:604307]. A congenital pulverulent disk-like opacity involving the embryonic nucleus with many tiny white dots in the lamellar portion of the lens. It is usually bilateral and dominantly inherited.
P07320	Defects in CRYGD are a cause of cataract autosomal dominant (ADC) [MIM:604219]. Cataract is an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. Cataract is the most common treatable cause of visual disability in childhood.
P07320	Defects in CRYGD are the cause of cataract congenital non-nuclear polymorphic autosomal dominant (CCP) [MIM:601286]; also known as polymorphic congenital cataract. A congenital cataract characterized by a non-progressive phenotype and partial opacity that has a variable location between the fetal nucleus of the lens and the equator. The fetal nucleus is normal. The opacities are irregular and look similar to a bunch of grapes and may be present simultaneously in different lens layers.
P07320	Defects in CRYGD are the cause of cataract congenital cerulean type 3 (CCA3) [MIM:608983]; also known as congenital cataract blue dot type 3. A cerulean form of autosomal dominant congenital cataract. Cerulean cataract is characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract.
P07320	Defects in CRYGD are the cause of cataract crystalline aculeiform (CACA) [MIM:115700]. A congenital crystalline cataract characterized by fiberglass-like or needle-like crystals projecting in different directions, through or close to the axial region of the lens. The opacity causes a variable degree of vision loss.
O75462	Defects in CRLF1 are the cause of cold-induced sweating syndrome type 1 (CISS1) [MIM:272430]. Cold-induced sweating syndrome (CISS) is an autosomal recessive disorder characterized by profuse sweating induced by cool surroundings (temperatures of 7 to 18 degrees Celsius). Additional abnormalities include a high- arched palate, nasal voice, depressed nasal bridge, inability to fully extend the elbows and kyphoscoliosis.
O75462	Defects in CRLF1 are the cause of Crisponi syndrome [MIM:601378]. Crisponi syndrome is a rare autosomal recessive disorder characterized by congenital muscular contractions of facial muscles, with trismus in response to stimuli, dysmorphic features, bilateral camptodactyly, major feeding and respiratory difficulties, and access of hyperthermia leading to death in the first months of life.
O75718	Defects in CRTAP are the cause of osteogenesis imperfecta type 7 (OI7) [MIM:610682]. OI is a connective tissue disorder characterized by bone fragility and low bone mass. OI7 is an autosomal recessive form of OI.
O75718	Defects in CRTAP are the cause of osteogenesis imperfecta type 2B (OI2B) [MIM:610854]. OI2B is an autosomal recessive form of perinatal lethal OI. This form is designated OI2B to distinguish it from the autosomal dominant form OI2A.
Q9CYD3	Defects in Crtap are a cause of osteochondrodysplasia characterized by severe osteoporosis and decreased osteoid production.
Q8N6W3	A chromosomal aberration involving CRTC1 is found in mucoepidermoid carcinomas, benign Warthin tumors and clear cell hidradenomas. Translocation t(11;19)(q21;p13) with MAML2. The fusion protein consists of the N-terminus of CRTC1 joined to the C-terminus of MAML2. The reciprocal fusion protein consisting of the N-terminus of MAML2 joined to the C-terminus of CRTC1 has been detected in a small number of mucoepidermoid carcinomas.
P82279	Defects in CRB1 are the cause of retinitis pigmentosa type 12 (RP12) [MIM:600105]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP12 is an autosomal recessive severe form characterized by a preserved paraarteriolar retinal pigment epithelium (PPRPE). RP12 occurs from early childhood and patients experiment progressive visual field loss with severe visual impairment before the age of twenty.
P82279	Defects in CRB1 are the cause of Leber congenital amaurosis type 8 (LCA8) [MIM:604210]. LCA designates a clinically and genetically heterogeneous group of childhood retinal degenerations, generally inherited in an autosomal recessive manner. Affected infants have little or no retinal photoreceptor function as tested by electroretinography. LCA represents the most common genetic cause of congenital visual impairment in infants and children.
P82279	Defects in CRB1 are the cause of pigmented paravenous chorioretinal atrophy (PPCRA) [MIM:172870]. PPCRA is an unusual retinal degeneration characterized by accumulation of pigmentation along retinal veins. PPCRA is dominantly inherited, but exhibited variable expressivity. Males are more likely to exhibit a severe phenotype, whereas females may remain virtually asymptomatic even in later years. The PPCRA phenotype is associated with a mutation in CRB1 gene which is likely to affect the structure of the CRB1 protein.
Q8VHS2	Defects in Crb1 are a cause of focal retinal dysplasia and degeneration associated with a shortening of inner and outer segments. Affected mice produce a secreted truncated protein that lacks the single transmembrane and the intracellular domain, and develop irregularities at the outer limiting membrane and loss of photoreceptor cells.
O43186	Defects in CRX are the cause of Leber congenital amaurosis type 7 (LCA7) [MIM:602225]. LCA designates a clinically and genetically heterogeneous group of childhood retinal degenerations, generally inherited in an autosomal recessive manner. Affected infants have little or no retinal photoreceptor function as tested by electroretinography. LCA represents the most common genetic cause of congenital visual impairment in infants and children.
O43186	Defects in CRX are the cause of cone-rod dystrophy type 2 (CORD2) [MIM:120970]; also known as cone-rod retinal dystrophy 2 (CRD2). CORDs are inherited retinal dystrophies belonging to the group of pigmentary retinopathies. CORDs are characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa.
O43186	Defects in CRX are a cause of retinitis pigmentosa (RP) [MIM:268000]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
P02489	Defects in CRYAA are a cause of cataract autosomal dominant (ADC) [MIM:604219]. Cataract is an opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. Cataract is the most common treatable cause of visual disability in childhood.
P02511	Defects in CRYAB are the cause of myofibrillar alpha-B crystallin-related (MFM-CRYAB) [MIM:608810]. A neuromuscular disorder that results in weakness of the proximal and distal limb muscles, weakness of the neck, velopharynx and trunk muscles, hypetrophic cardiomyopathy, and cataract in a subset of patients.
P07141	A defect in Csf1 is the cause of osteopetrosis. Osteopetrotic mice (op/op) are severely deficient in mature macrophages and osteoclasts, display failed tooth eruption, and have a restricted capacity for bone remodeling.
Q8JZQ0	A defect in Csf1 is the cause of the toothless phenotype (tl). Toothless rats display osteoclastopenia, severe osteopetrosis, and dystrophic growth plates.
P15509	Defects in CSF2RA are the cause of pulmonary surfactant metabolism dysfunction type 4 (SMDP4) [MIM:300770]. A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.
Q5VT18	Defects in CASK are the cause of mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) [MIM:300749]. MICPCH is characterized by severe mental retardation, microcephaly and disproportionate pontine and cerebellar hypoplasia.
Q5VT18	Defects in CASK are the cause of FG syndrome type 4 (FGS4) [MIM:300422]. FG syndrome (FGS) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation.
P13611	Defects in VCAN are the cause of Wagner syndrome type 1 (WGN1) [MIM:143200]. WGN is a dominantly inherited vitreoretinopathy characterized by an optically empty vitreous cavity with fibrillary condensations and a preretinal avascular membrane. Other optical features include progressive chorioretinal atrophy, perivascular sheating, subcapsular cataract and myopia. Systemic manifestations are absent in WGN.
P50461	Defects in CSRP3 are the cause of cardiomyopathy dilated type 1M (CMD1M) [MIM:607482]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
P50461	Defects in CSRP3 are the cause of cardiomyopathy familial hypertrophic type 12 (CMH12) [MIM:612124]. Familial hypertrophic cardiomyopathy is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
Q5TEU4	Defects in C20orf7 are a cause of mitochondrial complex I deficiency [MIM:252010]. Mitochondrial complex I deficiency is the most common cause of mitochondrial disorders. It represents largely one-third of all cases of respiratory chain deficiency and is responsible for a variety of clinical symptoms, ranging from neurological disorders to cardiomyopathy, liver failure, and myopathy. Mitochondrial complex I deficiency due to C20orf7 mutations is a lethal, neonatal form.
Q9Y5B0	Defects in CTDP1 are a cause of congenital cataracts facial dysmorphism and neuropathy syndrome (CCFDN) [MIM:604168]. CCFDN is an autosomal recessive developmental disorder that occurs in an endogamous group of Vlax Roma (Gypsies). The syndrome is characterized by a complex clinical phenotype with seemingly unrelated features involving multiple organs and systems. Developmental abnormalities include congenital cataracts and microcorneae, hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, facial dysmorphism and hypogonadism. Central nervous system involvement, with cerebral and spinal cord atrophy, may be the result of disrupted development with superimposed degenerative changes. Affected individuals are prone to severe rhabdomyolysis after viral infections and to serious complications related to general anesthesia (such as pulmonary edema and epileptic seizures).
O15320	Autoantibodies against CTAGE5 are present in several cancer types, including benign meningioma and cutaneous T-cell lymphoma (CTCL).
Q8TEW4	A chromosomal aberration involving CTL4 is a cause of sialidosis, a lysosomal storage disease [MIM:256550]. A rearrangement with NEU1 generates the CTL4-NEU1 transcript by fusing CTL4 to the 3'-end of NEU1.
P16410	Genetic variation in CTLA4 influences susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. SLE is a chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. SLE is thought to represent a failure of the regulatory mechanisms of the autoimmune system.
P16410	Genetic variation in CTLA4 may be a cause of susceptibility to Graves disease (GRD) [MIM:275000]. GRD is an autoimmune disorder causing overactivity of the thyroid gland and hyperthyroidism.
P16410	Genetic variation in CTLA4 is the cause of susceptibility to insulin-dependent diabetes mellitus type 12 (IDDM12) [MIM:601388].
P16410	Genetic variation in CTLA4 is the cause of susceptibility to celiac disease type 3 (CELIAC3) [MIM:609755]. Celiac disease [MIM:212750] is a multifactorial disorder of the small intestine that is influenced by both environmental and genetic factors. It is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins. In its classic form, celiac disease is characterized in children by malabsorption and failure to thrive.
P16410	Genetic variations in CTLA4 are associated with susceptibility to hepatitis B virus infection (HBV infection) [MIM:610424]. Approximately one third of all cases of cirrhosis and half of all cases of hepatocellular carcinoma can be attributed to chronic HBV infection. HBV infection may result in subclinical or asymptomatic infection, acute self-limited hepatitis, or fulminant hepatitis requiring liver transplantation.
P35222	Defects in CTNNB1 are associated with colorectal cancer (CRC) [MIM:114500].
P35222	Activating mutations in CTNNB1 have oncogenic activity resulting in tumor development. Somatic mutations are found in various tumor types, including colon cancers, ovarian and prostate carcinomas, hepatoblastoma (HB), hepatocellular carcinoma (HCC). HBs are malignant embryonal tumors mainly affecting young children in the first three years of life.
P35222	Defects in CTNNB1 are a cause of pilomatrixoma (PTR) [MIM:132600]; a common benign skin tumor.
P35222	Defects in CTNNB1 are a cause of medulloblastoma (MDB) [MIM:155255]. MDB is a malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children.
P35222	Defects in CTNNB1 are associated with ovarian cancer [MIM:167000]. Ovarian cancer is the leading cause of death from gynecologic malignancy. It is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases. These typical features relate to the biology of the disease, which is a principal determinant of outcome.
P35222	A chromosomal aberration involving CTNNB1 may be a cause of salivary gland pleiomorphic adenomas (PA) [181030]. Pleiomorphic adenomas are the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with PLAG1.
O60931	Defects in CTNS are the cause of cystinosis [MIM:219800, 219900, 219750]. This autosomal recessive disorder results from defective lysosomal transport of cystine. The classical nephropathic form is characterized by renal failure at 10 years of age and other systemic complications. Milder phenotype exist such as intermediate cystinosis, with later onset of renal disease and benign or non-nephropathic cystinosis, with symptoms related only to corneal crystals and photophobia.
Q99895	Variations in CTRC influence susceptibility to chronic pancreatitis [MIM:167800]. Chronic pancreatitis is a persistent inflammatory disorder characterized by permanent destruction of the pancreatic parenchyma.
Q96P56	Defects in CATSPER2 are a cause of deafness-infertility syndrome (DIS) [MIM:611102]. DIS is characterized by deafness and infertility and is caused by large contiguous gene deletions at 15q15.3 that removes both STRC and CATSPER2 genes.
O60494	Defects in CUBN are a cause of recessive hereditary megaloblastic anemia 1 (MGA1) [MIM:261100]; also known as MGA1 Norwegian type or Imerslund-Grasbeck syndrome (I-GS). MGA1 is due to selective malabsorption of vitamin B12. Defects in vitamin B12 absorption lead to impaired function of thymidine synthase. As a consequence DNA synthesis is interrupted. Rapidly dividing cells involved in erythropoiesis are particularly affected.
Q13620	Defects in CUL4B are the cause of mental retardation syndromic X-linked type 15 (MRXS15) [MIM:300639]. It is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. The distinguishing manifestations of MRXS15 are relative microcephaly, short stature, hypertelorism, macrostomia, patulous lips, difficulty in speech, micrognathia, short thumbs and little fingers with adduction, hypotonia at age less than 10 years, and later hypertonia, restlessness, and seizures. Obligate carrier females are clinically normal except for rather large hands with deep palmar and finger creases with rhagades.
Q13620	Defects in CUL4B are the cause of mental retardation syndromic X-linked Cabezas type (MRXC) [MIM:300354]. A syndromic form of X-linked mental retardation characterized by short stature, prominent lower lip, small testes, muscle wasting in lower legs, kyphosis, joint hyperextensibility, abnormal gait, tremor, and decreased fine motor coordination.
Q14999	Defects in CUL7 are the cause of 3M syndrome type 1 (3M1) [MIM:273750]. An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies.
P14854	Defects in COX6B1 are a cause of cytochrome c oxidase deficiency (COX deficiency) [MIM:220110]. A metabolic disorder with heterogeneous clinical manifestations, ranging from isolated myopathy to severe multisystem disease affecting several tissues and organs. Features include hypertrophic cardiomyopathy, hepatomegaly and liver dysfunction, hypotonia, muscle weakness, excercise intolerance, developmental delay, delayed motor development and mental retardation, lactic acidosis.
P17302	Defects in GJA1 are the cause of autosomal dominant oculodentodigital dysplasia (ODDD) [MIM:164200]; also known as oculodentoosseous dysplasia. ODDD is a highly penetrant syndrome presenting with craniofacial (ocular, nasal, dental) and limb dysmorphisms, spastic paraplegia, and neurodegeneration. Craniofacial anomalies tipically include a thin nose with hypoplastic alae nasi, small anteverted nares, prominent columnella, and microcephaly. Brittle nails and hair abnormalities of hypotrichosis and slow growth are present. Ocular defects include microphthalmia, microcornea, cataracts, glaucoma, and optic atrophy. Syndactyly type 3 and conductive deafness can occur in some cases. Cardiac abnormalities are observed in rare instances.
P17302	Defects in GJA1 are the cause of autosomal recessive oculodentodigital dysplasia (ODDD autosomal recessive) [MIM:257850].
P17302	Defects in GJA1 may be the cause of syndactyly type 3 (SDTY3) [MIM:186100]. Syndactyly is an autosomal dominant trait and is the most common congenital anomaly of the hand or foot. It is marked by persistence of the webbing between adjacent digits, so they are more or less completely attached. In this type there is usually complete and bilateral syndactyly between the fourth and fifth fingers. Usually it is soft tissue syndactyly but occasionally the distal phalanges are fused. The fifth finger is short with absent or rudimentary middle phalanx. The feet are not affected.
P17302	Defects in GJA1 are a cause of hypoplastic left heart syndrome (HLHS) [MIM:241550]. HLHS refers to the abnormal development of the left-sided cardiac structures, resulting in obstruction to blood flow from the left ventricular outflow tract. In addition, the syndrome includes underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral atresia or stenosis.
Q9Y6H8	Defects in GJA3 are the cause of cataract zonular pulverulent cataract type 3 (CZP3) [MIM:601885]. A form of zonular cataract. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes.
P36382	Defects in GJA5 are a cause of familial atrial standstill (FAS) [MIM:108770]. Atrial standstill is an extremely rare arrhythmia, characterized by the absence of electrical and mechanical activity in the atria. Electrocardiographically, it is characterized by bradycardia, the absence of P waves, and a junctional narrow complex escape rhythm.
P48165	Defects in GJA8 are the cause of cataract zonular pulverulent type 1 (CZP1) [MIM:116200]. A form of zonular cataract. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Zonular cataracts generally do not involve the embryonic nucleus, though sometimes they involve the fetal nucleus. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes.
P48165	Defects in GJA8 are the cause of cataract-microcornea syndrome [MIM:116150]. Cataract-microcornea syndrome is characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Clinical findings include a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye, and an inherited cataract, which is most often bilateral posterior polar with opacification in the lens periphery. The cataract progresses to form a total cataract after visual maturity has been achieved, requiring cataract extraction in the first to third decade of life. Microcornea-cataract syndrome can be associated with other rare ocular manifestations, including myopia, iris coloboma, sclerocornea and Peters anomaly. Transmission is in most cases autosomal dominant, but cases of autosomal recessive transmission have recently been described.
Q8K4Q9	Defects in Gja8 are the cause of cataract.
P08034	Defects in GJB1 are the cause of Charcot-Marie-Tooth disease X-linked type 1 (CMTX1) [MIM:302800]; also designated CMT- X. CMTX1 is a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot- Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies characterized by severely reduced motor nerve conduction velocities (NCVs) (less than 38m/s) and segmental demyelination and remyelination, and primary peripheral axonal neuropathies characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy. CMTX1 has both demyelinating and axonal features. Central nervous system involvement may occur.
P08034	Defects in GJB1 may contribute to the phenotype of Dejerine-Sottas syndrome (DSS) [MIM:145900]; also known as Dejerine-Sottas neuropathy (DSN) or hereditary motor and sensory neuropathy III (HMSN3). DSS is a severe degenerating neuropathy of the demyelinating Charcot-Marie-Tooth disease category, with onset by age 2 years. DSS is characterized by motor and sensory neuropathy with very slow nerve conduction velocities, increased cerebrospinal fluid protein concentrations, hypertrophic nerve changes, delayed age of walking as well as areflexia. There are both autosomal dominant and autosomal recessive forms of Dejerine- Sottas syndrome.
Q96AK0	Defects in GJB2 are the cause of non-syndromic sensorineural deafness autosomal recessive type 1A (DFNB1A) [MIM:220290]. DFNB1A is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Q96AK0	Defects in GJB2 are the cause of non-syndromic sensorineural deafness autosomal dominant type 3A (DFNA3A) [MIM:601544].
Q96AK0	Defects in GJB2 are a cause of Vohwinkel syndrome (VS) [MIM:124500]. VS is an autosomal dominant disease characterized by hyperkeratosis, constriction on finger and toes and congenital deafness.
Q96AK0	Defects in GJB2 are a cause of palmoplantar keratoderma with deafness (PPKDFN) [MIM:148350]. PPKDFN is an autosomal dominant disorder characterized by the association of palmoplantar hyperkeratosis with progressive, bilateral, high-frequency, sensorineural deafness.
Q96AK0	Defects in GJB2 are a cause of keratitis-ichthyosis- deafness syndrome (KID syndrome) [MIM:148210]; an autosomal dominant form of ectodermal dysplasia. Ectodermal dysplasias (EDs) constitute a heterogeneous group of developmental disorders affecting tissues of ectodermal origin. EDs are characterized by abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. KID syndrome is characterized by the association of hyperkeratotic skin lesions with vascularizing keratitis and profound sensorineural hearing loss. Clinical features include deafness, ichthyosis, photobia, absent or decreased eyebrows, sparse or absent scalp hair, decreased sweating and dysplastic finger and toenails.
Q96AK0	Defects in GJB2 are the cause of Bart-Pumphrey syndrome (BPS) [MIM:149200]. BPS is an autosomal dominant disorder characterized by sensorineural hearing loss, palmoplantar keratoderma, knuckle pads, and leukonychia, It shows considerable phenotypic variability.
Q96AK0	Defects in GJB2 are the cause of ichthyosis hystrix-like with deafness syndrome (HID syndrome) [MIM:602540]. HID syndrome is an autosomal-dominant inherited keratinizing disorder characterized by sensorineural deafness and spiky hyperkeratosis affecting the entire skin. HID syndrome is considered to differ from the similar KID syndrome in the extent and time of occurrence of skin symptoms and the severity of the associated keratitis.
O75712	Defects in GJB3 are a cause of erythrokeratodermia variabilis (EKV) [MIM:133200]. EKV is a genodermatosis characterized by the appearance of two independent skin lesions: transient figurate erythematous patches and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases.
O75712	Defects in GJB3 are the cause of non-syndromic sensorineural deafness autosomal dominant type 2B (DFNA2B) [MIM:612644]. DFNA2 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Q9NTQ9	Defects in GJB4 are a cause of erythrokeratodermia variabilis (EKV) [MIM:133200]. EKV is a genodermatosis characterized by the appearance of two independent skin lesions: transient figurate erythematous patches and hyperkeratosis that is usually localized but occasionally occurs in its generalized form. Clinical presentation varies significantly within a family and from one family to another. Palmoplantar keratoderma is present in around 50% of cases.
O95452	Defects in GJB6 are the cause of ectodermal dysplasia type 2 (ED2) [MIM:129500]; also known as Clouston syndrome. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. ED2 is an autosomal dominant condition characterized by atrichosis, nail hypoplasia and deformities, hyperpigmentation of the skin, normal teeth, normal sweat and sebaceous gland function. Palmoplantar hyperkeratosis is a frequent features. Hearing impairment has been detected in few cases of ED2.
O95452	Defects in GJB6 are the cause of non-syndromic sensorineural deafness autosomal recessive type 1B (DFNB1B) [MIM:612645]. DFNB1B is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
O95452	Defects in GJB6 are the cause of non-syndromic sensorineural deafness autosomal dominant type 3B (DFNA3B) [MIM:612643].
P61073	Defects in CXCR4 are a cause of WHIM syndrome [MIM:193670]; also known as warts, hypogammaglobulinemia, infections and myelokathexis. WHIM syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis.
Q5T442	Defects in GJC2 are the cause of Leukodystrophy hypomyelinating type 2 (HLD2) [MIM:608804]; also known as Pelizaeus-Merzbacher-like disease autosomal recessive type 1. HLD2 is an autosomal recessive hypomyelinating leukodystrophy characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria and progressive spasticity.
P13498	Defects in CYBA are a cause of chronic granulomatous disease autosomal recessive cytochrome-b-negative (ARCGD) [MIM:233690]. Chronic granulomatous disease is a genetically heterogeneous disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.
P04839	Defects in CYBB are a cause of chronic granulomatous disease X-linked (XCGD) [MIM:306400]. Chronic granulomatous disease is a genetically heterogeneous disorder characterized by the inability of neutrophils and phagocytes to kill microbes that they have ingested. Patients suffer from life-threatening bacterial/fungal infections.
P00167	Defects in CYB5A are the cause of type IV hereditary methemoglobinemia [MIM:250790].
Q9B2X7	Defects in MT-CYB are a rare cause of mitochondrial dysfunction underlying different myopathies. They include mitochondrial encephalomyopathy, hypertrophic cardiomyopathy (HCM), and sporadic mitochondrial myopathy (MM). In mitochondrial myopathy, exercise intolerance is the predominant symptom. Additional features include lactic acidosis, muscle weakness and/or myoglobinuria. Defects in MTCYB are also found in cases of exercise intolerance accompanied by deafness, mental retardation, retinitis pigmentosa, cataract, growth retardation, epilepsy (multisystem disorder).
Q9B2X7	Defects in MT-CYB are the cause of cardiomyopathy infantile histiocytoid (CMIH) [MIM:500000]. CMIH is characterized by the presence of pale granular foamy histiocyte-like cells within the myocardium. It usually affects children younger than 2 years of age, with a clear predominance of females over males. Infants present with dysrhythmia or cardiac arrest, and the clinical course is usually fulminant, sometimes simulating sudden infant death syndrome.
Q9B2X7	Defects in MT-CYB contribute to Leber hereditary optic neuropathy (LHON) [MIM:535000]. LHON is a maternally inherited disease resulting in acute or subacute loss of central vision, due to optic nerve dysfunction. Cardiac conduction defects and neurological defects have also been described in some patients. LHON results from primary mitochondrial DNA mutations affecting the respiratory chain complexes.
P99999	Defects in CYCS are the cause of thrombocytopenia type 4 (THC4) [MIM:612004]; also known as autosomal dominant thrombocytopenia type 4. Thrombocytopenia is the presence of relatively few platelets in blood. THC4 is a non-syndromic form of thrombocytopenia. Clinical manifestations of thrombocytopenia are absent or mild. THC4 may be caused by dysregulated platelet formation.
Q9NQC7	Defects in CYLD are the cause of familial cylindromatosis [MIM:132700]; also known as Ancell-Spiegler cylindromas or turban tumor syndrome or dermal eccrine cylindromatosis. CYLD is an autosomal dominant and highly tumor type-specific disorder. The tumors (known as cylindromas because of their characteristic microscopic architecture) are believed to arise from or recapitulate the appearance of the eccrine or apocrine cells of the skin that secrete sweat and scent respectively. Cylindromas arise predominantly in hairy parts of the body with approximately 90% on the head and neck. The development of a confluent mass which may ulcerate or become infected has led to the designation 'turban tumor syndrome'. The skin tumors show differentiation in the direction of hair structures, hence the synonym trichoepithelioma.
Q9NQC7	Defects in CYLD are the cause of multiple familial trichoepithelioma type 1 (MFT1) [MIM:601606]; also known as epithelioma adenoides cysticum of Brooke (EAC) or hereditary multiple benign cystic epithelioma or Brooke-Fordyce trichoepitheliomas. MFT1 is an autosomal dominant dermatosis characterized by the presence of many skin tumors predominantly on the face. Since histologic examination shows dermal aggregates of basaloid cells with connection to or differentiation toward hair follicles, this disorder has been thought to represent a benign hamartoma of the pilosebaceous apparatus. Trichoepitheliomas can degenerate into basal cell carcinoma.
Q9NQC7	Defects in CYLD are the cause of Brooke-Spiegler syndrome (BRSS) [MIM:605041]. BRSS is an autosomal dominant disorder characterized by the appearance of multiple skin appendage tumors such as cylindroma, trichoepithelioma, and spiradenoma. These tumors are typically located in the head and neck region, appear in early adulthood, and gradually increase in size and number throughout life.
Q8R4T1	Defects in Cys1 are a cause of polycystic kidney disease.
P04080	Defects in CSTB are the cause of progressive myoclonic epilepsy type 1 (EPM1) [MIM:254800]. EPM1 is an autosomal recessive disorder characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures. The onset, occurring between 6 and 13 years of age, is characterized by convulsions. Myoclonus begins 1 to 5 years later. The twitchings occur predominantly in the proximal muscles of the extremities and are bilaterally symmetrical, although asynchronous. At first small, they become late in the clinical course so violent that the victim is thrown to the floor. Mental deterioration and eventually dementia develop.
P01034	Defects in CST3 are the cause of amyloidosis type 6 (AMYL6) [MIM:105150]; also known as hereditary cerebral hemorrhage with amyloidosis (HCHWA), cerebral amyloid angiopathy (CAA) or cerebroarterial amyloidosis Icelandic type. AMYL6 is a hereditary generalized amyloidosis due to cystatin C amyloid deposition. Cystatin C amyloid accumulates in the walls of arteries, arterioles, and sometimes capillaries and veins of the brain, and in various organs including lymphoid tissue, spleen, salivary glands, and seminal vesicles. Amyloid deposition in the cerebral vessels results in cerebral amyloid angiopathy, cerebral hemorrhage and premature stroke. Cystatin C levels in the cerebrospinal fluid are abnormally low.
P01034	Genetic variations in CST3 are associated with age- related macular degeneration type 11 (ARMD11) [MIM:611953]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
Q5M773	A chromosomal aberration involving CYTSB may be a cause of juvenile myelomonocytic leukemia. Translocation t(5;17)(q33;p11.2) with PDGFRB.
Q8N465	Defects in D2HGDH are the cause of D-2-hydroxyglutaric aciduria (D2HGA) [MIM:600721]. D2HGA is a rare recessive neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. Both a mild and a severe phenotype exist. The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and cardiomyopathy. The mild phenotype has a more variable clinical presentation. Diagnosis is based on the presence of an excess of D-2-hydroxyglutaric acid in the urine.
Q5VWQ8	A chromosomal aberration involving DAB2IP is found in a patient with acute myeloid leukemia (AML). Translocation t(9;11)(q34;q23) with MLL. May give rise to a MLL-DAB2IP fusion protein lacking the PH domain.
Q9NQZ3	AZFc deletions in the Yq11.23 region including the DAZ genes are a cause of spermatogenic failure non-obstructive Y- linked (SFNOY) [MIM:415000]. A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility.
Q13117	AZFc deletions in the Yq11.23 region including the DAZ genes are a cause of spermatogenic failure non-obstructive Y- linked (SFNOY) [MIM:415000]. A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility.
Q9NR90	AZFc deletions in the Yq11.23 region including the DAZ genes are a cause of spermatogenic failure non-obstructive Y- linked (SFNOY) [MIM:415000]. A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility.
Q86SG3	AZFc deletions in the Yq11.23 region including the DAZ genes are a cause of spermatogenic failure non-obstructive Y- linked (SFNOY) [MIM:415000]. A disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility.
Q5H9S7	Defects in DCAF17 are the cause of Woodhouse-Sakati syndrome (WSS) [MIM:241080]. WSS is a rare autosomal recessive disorder characterized by hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome.
Q99259	Defects in GAD1 are the cause of autosomal recessive symmetric spastic cerebral palsy (SCP) [MIM:603513]. Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 250 to 1'000 live births, making CP one the commonest congenital disabilities. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. Patients present developmental delay, mental retardation and sometimes epilepsy as part of the phenotype.
O95822	Defects in MLYCD are the cause of malonyl-CoA decarboxylase deficiency (MLYCD deficiency) [MIM:248360]. MLYCD deficiency is an autosomal recessive disease characterized by abdominal pain, chronic constipation, episodic vomiting, metabolic acidosis and malonic aciduria.
Q5JSS7	Defects in DCLRE1C are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell- negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:602450]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T- cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity.
Q5JSS7	Defects in DCLRE1C are the cause of severe combined immunodeficiency Athabaskan type (SCIDA) [MIM:602450]. SCIDA is a variety of RS-SCID caused by a founder mutation in Athabascan- speaking native Americans, being inherited as an autosomal recessive trait with an estimated gene frequency of 2.1% in the Navajo population. Affected individuals exhibit clinical symptoms and defects in DNA repair comparable to those seen in RS-SCID.
Q5JSS7	Defects in DCLRE1C are a cause of Omenn syndrome (OS) [MIM:603554]. OS is characterized by severe combined immunodeficiency associated with erythrodermia, hepatosplenomegaly, lymphadenopathy and alopecia. Affected individuals have elevated T-lymphocyte counts with a restricted T- cell receptor (TCR) repertoire. They also generally lack B- lymphocytes, but have normal natural killer (NK) cell function (T+ B- NK+).
Q14203	Defects in DCTN1 are the cause of distal hereditary motor neuronopathy type 7B (HMN7B) [MIM:607641] also known as progressive lower motor neuron disease (PLMND). HMN7B is a neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs.
P06132	Defects in UROD are the cause of familial porphyria cutanea tarda (FPCT) [MIM:176100]; also known as porphyria cutanea tarda type II. FPCT is an autosomal dominant disorder characterized by light-sensitive dermatitis, with onset in later life. It is associated with the excretion of large amounts of uroporphyrin in the urine. Iron overload is often present in association with varying degrees of liver damage. Besides the familial form of PCT, a relatively common idiosyncratic form is known in which only the liver enzyme is reduced. This form is referred to as porphyria cutanea tarda "sporadic " type or type I [MIM:176090]. PCT type I occurs sporadically as an unusual accompaniment of common hepatic disorders such as alcohol- associated liver disease.
P06132	Defects in UROD are the cause of hepatoerythropoietic porphyria (HEP) [MIM:176100]. HEP is a rare autosomal recessive disorder. It is the severe form of cutaneous porphyria, and presents in infancy. The level of UROD is very low in erythrocytes and cultured skin fibroblasts, suggesting that HEP is the homozygous state for porphyria cutanea tarda.
Q8HY31	Defects in UROD are the cause of porphyria cutanea tarda (PCT). PCT has been identified in a flock of German Blackface sheep. It is characterized by photosensitivity and porphyrinuria.
Q7Z4W1	Defects in DCXR are a cause of pentosuria [MIM:260800]; also known as L-xylulosuria or xylitol dehydrogenase deficiency. Pentosuria is an inborn error of carbohydrate metabolism, characterized by the excessive urinary excretion of the sugar xylitol.
O43602	Defects in DCX are the cause of lissencephaly X-linked type 1 (LISX1) [MIM:300067]; also called X-LIS or LIS. LISX1 is a classic lissencephaly characterized by mental retardation and seizures that are more severe in male patients. Affected boys show an abnormally thick cortex with absent or severely reduced gyri. Clinical manifestations include feeding problems, abnormal muscular tone, seizures and severe to profound psychomotor retardation. Female patients display a less severe phenotype referred to as 'doublecortex'.
O43602	Defects in DCX are the cause of subcortical band heterotopia X-linked (SBHX) [MIM:300067]; also known as double cortex or subcortical laminar heterotopia (SCLH). SBHX is a mild brain malformation of the lissencephaly spectrum. It is characterized by bilateral and symmetric plates or bands of gray matter found in the central white matter between the cortex and cerebral ventricles, cerebral convolutions usually appearing normal.
O43602	A chromosomal aberration involving DCX is found in lissencephaly. Translocation t(X;2)(q22.3;p25.1).
Q92466	Defects in DDB2 are a cause of xeroderma pigmentosum complementation group E (XP-E) [MIM:278740]; also known as xeroderma pigmentosum V (XP5). XP-E is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities.
P20711	Defects in DDC are the cause of aromatic L-amino-acid decarboxylase deficiency (AADCD) [MIM:608643]. AADCD deficiency is an inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency. It causes developmental and psychomotor delay, poor feeding, lethargy, ptosis, intermittent hypothermia, gastrointestinal disturbances. The onset is early in infancy and inheritance is autosomal recessive.
P35638	A chromosomal aberration involving DDIT3 is found in a form of malignant myxoid liposarcoma [MIM:126337]. Translocation t(12;16)(q13;p11) with FUS.
O15523	DDX3Y is deleted in severe non-obstructive hypospermatogenesis [MIM:400042].
P26196	A chromosomal aberration involving DDX6 may be a cause of hematopoietic tumors such as B-cell lymphomas. Translocation t(11;14)(q23;q32).
Q8C2K1	Defects in Def6 results in spontaneous development of a lupus-like syndrome in aging female mice. It is characterized by the accumulation of effector/memory T-cells and IgG B-cells, profound hypergammaglobulinemia, autoantibody production, and glomerulonephritis.
P35659	A chromosomal aberration involving DEK is found in a subset of acute myeloid leukemia (AML); also known as acute non- lymphocytic leukemia. Translocation t(6;9)(p23;q34) with NUP214/CAN. It results in the formation of a DEK-CAN fusion gene.
Q8TD99	Defects in DES are the cause of myopathy myofibrillar desmin-related (MFM-DES) [MIM:601419]; also known as desmin- related myopathy (DRM). A neuromuscular disorder characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias, restrictive heart failure, and by myofibrillar destruction with intracytoplasmic accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells.
Q8TD99	Defects in DES are the cause of cardiomyopathy dilated type 1I (CMD1I) [MIM:604765]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Q8TD99	Defects in DES are the cause of neurogenic scapuloperoneal syndrome Kaeser type (Kaeser syndrome) [MIM:181400]. Kaeser syndrome is an autosomal dominant disorder with a peculiar scapuloperoneal distribution of weakness and atrophy. A large clinical variability is observed ranging from scapuloperoneal, limb grindle and distal phenotypes with variable cardiac or respiratory involvement. Facial weakness, dysphagia and gynaecomastia are frequent additional symptoms. Affected men seemingly bear a higher risk of sudden, cardiac death as compared to affected women. Histological and immunohistochemical examination of muscle biopsy specimens reveal a wide spectrum of findings ranging from near normal or unspecific pathology to typical, myofibrillar changes with accumulation of desmin.
P15924	Defects in DSP are the cause of palmoplantar keratoderma striate type 2 (SPPK2) [MIM:612908]; also known as keratosis palmoplantaris striata II. SPPK2 is characterized by skin thickening in the palms (linear pattern) and the soles (island- like pattern) and flexor aspect of the fingers. Abnormalities of the nails, the teeth and the hair are rarely present.
P15924	Defects in DSP are the cause of cardiomyopathy dilated with woolly hair and keratoderma (DCWHK) [MIM:605676]; also known as Carvajal syndrome or palmoplantar keratoderma with left ventricular cardiomyopathy and woolly hair. DCWHK is an autosomal recessive cardiocutaneous syndrome characterized by a generalized striate keratoderma particularly affecting the palmoplantar epidermis, woolly hair, and dilated left ventricular cardiomyopathy.
P15924	Defects in DSP are the cause of familial arrhythmogenic right ventricular dysplasia type 8 (ARVD8) [MIM:607450]; also known as arrhythmogenic right ventricular cardiomyopathy 8 (ARVC8). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall.
P15924	Defects in DSP are the cause of skin fragility-woolly hair syndrome (SFWHS) [MIM:607655]. SFWHS is an autosomal recessive genodermatosis characterized by focal and diffuse palmoplantar keratoderma, hyperkeratotic plaques on the trunk and limbs, and woolly hair with varying degrees of alopecia.
P15924	Defects in DSP are the cause of epidermolysis bullosa lethal acantholytic (EBLA) [MIM:609638]. EBLA is characterized by severe fragility of skin and mucous membranes. The phenotype is lethal in the neonatal period because of immense transcutaneous fluid loss. Typical features include universal alopecia, neonatal teeth, and nail loss. Histopathology of the skin shows suprabasal clefting and acantholysis throughout the spinous layer, mimicking pemphigus.
O60443	Defects in DFNA5 are the cause of non-syndromic sensorineural deafness autosomal dominant type 5 (DFNA5) [MIM:600994]. DFNA5 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Q16854	Defects in DGUOK are a cause of hepatocerebral mitochondrial DNA depletion syndrome (MDS) [MIM:251880]. MDS is a clinically heterogeneous group of disorders characterized by a reduction in mitochondrial DNA (mtDNA) copy number. Primary mtDNA depletion is inherited as an autosomal recessive trait and may affect single organs, typically muscle or liver, or multiple tissues. Individuals with the hepatocerebral form of mitochondrial DNA depletion syndrome have early progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids.
P37058	Defects in HSD17B3 are the cause of male pseudohermaphrodism with gynecomastia (MPH) [MIM:264300]. These individuals have unambiguous female external genitalia at birth, but fail to menstruate at the time of expected puberty and instead virilize as evidenced by growth of the phallus. Breast development may or may not take place.
P51659	Defects in HSD17B4 are a cause of D-bifunctional protein deficiency (DBPD) [MIM:261515]. DBPD is a disorder of peroxisomal fatty acid beta-oxidation.
Q15392	Defects in DHCR24 are the cause of desmosterolosis [MIM:602398]. It is a rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells.
Q9UBM7	Defects in DHCR7 are the cause of Smith-Lemli-Opitz syndrome (SLOS) [MIM:270400]; also known as SLO syndrome or RSH syndrome. SLOS is an autosomal recessive frequent inborn disorder of sterol metabolism with characteristic congenital malformations and dysmorphias. All patients suffer from mental retardation. Children with SLOS have elevated serum 7-dehydrocholesterol (7- DHC) levels and low serum cholesterol levels. SLOS occurs in relatively high frequency: approximately 1 in 20,000 to 30,000 births in populations of northern and central European background. Historically, a clinical distinction often was made between classic ('type I') SLOS and the more severely affected ('type II') patients. There is, in reality, a clinical and biochemical continuum from mild to severe SLOS.
P00367	Defects in GLUD1 are the cause of hyperinsulinism- hyperammonemia syndrome (HHS) [MIM:606762]. Elevated oxidation rate of glutamate to alpha-ketoglutarate stimulates insulin secretion in the pancreatic beta cells, while they impair detoxification of ammonium in the liver.
O43323	Defects in DHH may be the cause of partial gonadal dysgenesis with minifascicular neuropathy 46,XY (PGD) [MIM:607080]. PGD is characterized by the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity.
O43323	Defects in DHH may be the cause of complete pure gonadal dysgenesis 46,XY type (GDXYM) [MIM:233420]; also known as male- limited gonadal dysgenesis 46,XY. GDXYM is a type of hypogonadism in which no functional gonads are present to induce puberty in an externally female person whose karyotype is then found to be XY. The gonads are found to be non-functional streaks.
P28845	Defects in HSD11B1 are a cause of cortisone reductase deficiency (CRD) [MIM:604931]. In CRD, activation of cortisone to cortisol does not occur, resulting in adrenocorticotropin-mediated androgen excess and a phenotype resembling polycystic ovary syndrome (PCOS).
Q9UC51	Defects in HSD11B2 are the cause of apparent mineralocorticoid excess (AME) [MIM:218030]. AME is a potentially fatal disease characterized by severe juvenile low-renin hypertension, sodium retention, hypokalemia and low levels of aldosterone. It often leads to nephrocalcinosis.
P09417	Defects in QDPR are the cause of BH4-deficient hyperphenylalaninemia type C (HPABH4C) [MIM:261630]; also called dihydropteridine reductase deficiency (DHPR deficiency) or hyperphenylalaninemia tetrahydrobiopterin-deficient due to DHPR deficiency or quinoid dihydropteridine reductase deficiency (QDPR deficiency). HPABH4C is a rare autosomal recessive disorder characterized by hyperphenylalaninemia and severe neurologic symptoms (malignant hyperphenylalaninemia) including axial hypotonia and truncal hypertonia, abnormal thermogenesis, and microcephaly. These signs are attributable to depletion of the neurotransmitters dopamine and serotonin, whose syntheses are controlled by tryptophan and tyrosine hydroxylases that use BH-4 as cofactor. These patients do not respond to phenylalanine- restricted diet. HPABH4C is lethal if untreated.
P31040	Defects in SDHA are a cause of complex II mitochondrial respiratory chain deficiency [MIM:252011]; also known as succinate CoQ reductase deficiency. Defects of oxidative phosphorylation give rise to heterogeneous clinical symptoms ranging from isolated organ dysfunction to multisystem disorder. A deficiency of complex II represents a rare cause of mitochondrial encephalomyopathy, leukodystrophy, late-onset optic atrophy and ataxia, myopathy with exercise intolerance, and isolated cardiomyopathy.
P31040	Defects in SDHA are a cause of Leigh syndrome (LS) [MIM:256000]. LS is a severe disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions.
P21912	Defects in SDHB are a cause of pheochromocytoma [MIM:171300]. The pheochromocytomas are catecholamine-producing, chromaffin tumors that arise in the adrenal medulla in 90% of cases. In the remaining 10% of cases, they develop in extra- adrenal sympathetic ganglia and may be referred to as "paraganglioma." Pheochromocytoma usually presents with hypertension. Approximately 10% of pheochromocytoma is hereditary. Although pheochromocytoma susceptibility may be associated with germline mutations in the tumor-suppressor genes VHL and NF1 and in the proto-oncogene RET, the genetic basis for most cases of non-syndromic familial pheochromocytoma is unknown.
P21912	Defects in SDHB are the cause of hereditary paragangliomas type 4 (PLG4) [MIM:115310]; also known as familial non-chromaffin paragangliomas type 4. Paragangliomas refer to rare and mostly benign tumors that arise from any component of the neuroendocrine system. PLG4 is characterized by the development of mostly benign, highly vascular, slow growing tumors in the head and neck. In the head and neck region, the carotid body is the largest of all paraganglia and is also the most common site of the tumors.
P21912	Defects in SDHB are a cause of paraganglioma and gastric stromal sarcoma [MIM:606864]; also called Carney-Stratakis syndrome. Gastrointestinal stromal tumors may be sporadic or inherited in an autosomal dominant manner, alone or as a component of a syndrome associated with other tumors, such as in the context of neurofibromatosis type 1 (NF1). Patients have both gastrointestinal stromal tumors and paragangliomas. Susceptibility to the tumors was inherited in an apparently autosomal dominant manner, with incomplete penetrance.
P21912	Defects in SDHB are a cause of Cowden-like syndrome [MIM:612359]. Cowden-like syndrome is a cancer predisposition syndrome associated with elevated risk for tumors of the breast, thyroid, kidney and uterus.
O14521	Defects in SDHD are a cause of hereditary paragangliomas type 1 (PGL1) [MIM:168000]; also known as familial non-chromaffin paragangliomas type 1. Paragangliomas refer to rare and mostly benign tumors that arise from any component of the neuroendocrine system. PGL1 is a rare autosomal dominant disorder which is characterized by the development of mostly benign, highly vascular, slowly growing tumors in the head and neck. In the head and neck region, the carotid body is the largest of all paraganglia and is also the most common site of the tumors. Penetrance of PLG1 is incomplete when the disease is transmitted through fathers. No disease phenotype is transmitted maternally.
O14521	Defects in SDHD are a cause of pheochromocytoma [MIM:171300]. The pheochromocytomas are catecholamine-producing, chromaffin tumors that arise in the adrenal medulla in 90% of cases. In the remaining 10% of cases, they develop in extra- adrenal sympathetic ganglia and may be referred to as 'paraganglioma'. Pheochromocytoma usually presents with hypertension. Approximately 10% of pheochromocytoma is hereditary. Although pheochromocytoma susceptibility may be associated with germline mutations in the tumor-suppressor genes VHL and NF1 and in the proto-oncogene RET, the genetic basis for most cases of non-syndromic familial pheochromocytoma is unknown.
O14521	Defects in SDHD are involved in intestinal carcinoid tumor [MIM:114900]. A carcinoid tumor is a yellow circumscribed tumor arising from enterochromaffin cells, in the small intestine.
O14521	Defects in SDHD are a cause of paraganglioma and gastric stromal sarcoma [MIM:606864]; also called Carney-Stratakis syndrome. Gastrointestinal stromal tumors may be sporadic or inherited in an autosomal dominant manner, alone or as a component of a syndrome associated with other tumors, such as in the context of neurofibromatosis type 1 (NF1). Patients have both gastrointestinal stromal tumors and paragangliomas. Susceptibility to the tumors was inherited in an apparently autosomal dominant manner, with incomplete penetrance.
O14521	Defects in SDHD are a cause of Cowden-like syndrome [MIM:612359]. Cowden-like syndrome is a cancer predisposition syndrome associated with elevated risk for tumors of the breast, thyroid, kidney and uterus.
O60610	Defects in DIAPH1 are the cause of non-syndromic sensorineural deafness autosomal dominant type 1 (DFNA1) [MIM:124900]. DFNA1 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
O60879	Defects in DIAPH2 are a cause of premature ovarian failure type 2 (POF2) [MIM:300511]. Premature ovarian failure (POF) is a defect of ovarian development and is characterized by hypoestrogenism, primary or secondary amenorrhea, with elevated levels of serum gonadotropins, or by early menopause. POF is defined as the cessation of ovarian function under the age of 40 years. The disorder has been attributed to various causes, including rearrangements of a large 'critical region' in the long arm of the X chromosome.
Q969H9	A chromosomal aberration involving DIRC1 is found in familial renal cell carcinoma type 1 (RCC1) [MIM:144700]. Translocation t(2;3)(q33;q21).
Q96SL1	A chromosomal aberration involving DIRC2 is found in familial renal cell carcinoma type 1 (RCC1) [MIM:144700]. Translocation t(2;3)(q35;q21).
Q9NRI4	A chromosomal aberration involving DISC1 segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Translocation t(1;11)(q42.1;q14.3). The truncated DISC1 protein produced by this translocation is unable to interact with ATF4, ATF5 and NDEL1.
Q9NRI4	Genetic variation in DISC1 is associated with susceptibility to schizophrenia type 9 (SCZD9) [MIM:604906]. A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder.
O60832	Defects in DKC1 are a cause of dyskeratosis congenita X- linked recessive (XDKC) [MIM:305000]. XDKC is a rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy.
O60832	Defects in DKC1 are the cause of Hoyeraal-Hreidarsson syndrome (HHS) [MIM:300240]. HHS is a multisystem disorder affecting males and is characterized by aplastic anemia, immunodeficiency, microcephaly, cerebellar hypoplasia, and growth retardation.
P09622	Defects in DLD are a cause of congenital infantile lactic acidosis.
P09622	Defects in DLD are a cause of maple syrup urine disease (MSUD) [MIM:248600]. MSUD is characterized by mental and physical retardation, feeding problems and a maple syrup odor to the urine. The keto acids of the branched-chain amino acids are present in the urine, resulting from a block in oxidative decarboxylation.
Q9Y238	Defects in DLEC1 may be a cause of primary lung cancer [MIM:211980]. In 33% of lung, esophageal and renal cancer cell lines and primary cancers, there is a lack of functional transcripts and an increase in alternatively spliced non- functional transcripts; the gene itself is not altered.
Q9Y238	Defects in DLEC1 may be a cause of esophageal cancer [MIM:133239].
Q9Y238	Defects in DLEC1 may be a cause of renal cancer.
Q9Y238	Defects in DLEC1 may be a cause of breast cancer.
Q92796	Defects in DLG3 are the cause of mental retardation X- linked type 90 (MRX90) [MIM:300189]. Mental retardation is characterized by significantly sub-average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs.
Q9NYJ7	Defects in DLL3 are the cause of spondylocostal dysostosis autosomal recessive type 1 (SCDO1) [MIM:277300]. Autosomal recessive spondylocostal dysostosis is a rare condition of variable severity associated with vertebral and rib segmentation defects. The main skeletal malformations include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and other rib malformations. Deformity of the chest and spine (severe scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the malformation and leads to a dwarf-like appearance. As the thorax is small, infants frequently have respiratory insufficiency and repeated respiratory infections resulting in life-threatening complications in the first year of life.
O88516	A truncating mutation in Dll3 is the cause of the pudgy (pu) phenotype. Pudgy mice exhibit patterning defects at the earliest stages of somitogenesis. Adult pudgy mice present severe vertebral and rib deformities.
Q86YH6	Defects in PDSS2 are a cause of coenzyme Q10 deficiency [MIM:607426]. Coenzyme Q10 deficiency is an autosomal recessive disorder with variable manifestations. It can be associated with three main clinical phenotypes: a predominantly myopathic form with central nervous system involvement, an infantile encephalomyopathy with renal dysfunction and an ataxic form with cerebellar atrophy.
O60479	Defects in DLX3 are a cause of trichodentoosseous syndrome (TDO) [MIM:190320]. TDO is an autosomal dominant syndrome characterized by enamel hypoplasia and hypocalcification with associated strikingly curly hair.
O60479	Defects in DLX3 are the cause of amelogenesis imperfecta type 4 (AI4) [MIM:104510]; also known as amelogenesis imperfecta hypomaturation-hypoplastic type with taurodontism. AI4 is an autosomal dominant defect of enamel formation associated with enlarged pulp chambers.
Q9Y4V9	Defects in DMBT1 are the cause of glioma of the brain [MIM:137800]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas.
Q9Y4V9	Inactivation of DMBT1 plays an important role in carcinogenesis. A loss or reduction of DMBT1 expression was seen in esophageal, gastric, lung and colorectal carcinomas. Deleted in medulloblastoma and glioblastoma cell lines. Homozygous deletions may be the predominant mechanism of inactivation.
Q9Y4V9	A deletion allele of DMBT1 which lacks five of the SRCR domains is associated with an increased risk of Crohn disease.
P11532	Defects in DMD are the cause of Duchenne muscular dystrophy (DMD) [MIM:310200]. DMD is the most common form of muscular dystrophy; a sex-linked recessive disorder. It typically presents in boys aged 3 to 7 year as proximal muscle weakness causing waddling gait, toe-walking, lordosis, frequent falls, and difficulty in standing up and climbing up stairs. The pelvic girdle is affected first, then the shoulder girdle. Progression is steady and most patients are confined to a wheelchair by age of 10 or 12. Flexion contractures and scoliosis ultimately occur. About 50% of patients have a lower IQ than their genetic expectations would suggest. There is no treatment.
P11532	Defects in DMD are the cause of Becker muscular dystrophy (BMD) [MIM:300376]. BMD resembles DMD in hereditary and clinical features but is later in onset and more benign.
P11532	Defects in DMD are a cause of cardiomyopathy dilated X- linked type 3B (CMD3B) [MIM:302045]; also known as X-linked dilated cardiomyopathy (XLCM). Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Q13316	Defects in DMP1 are the cause of autosomal recessive hypophosphatemic rickets (ARHR) [MIM:241520]. ARHR is characterized by rickets, osteomalacia, elevated FGF23 serum levels and hypophosphatemia.
Q8IXL6	Defects in FAM20C are the cause of Raine syndrome (RNS) [MIM:259775]. RNS is an autosomal recessive osteosclerotic bone dysplasia with neonatal lethal outcome. Clinical features include generalized osteosclerosis, craniofacial dysplasia and microcephaly.
Q09013	Defects in DMPK are the cause of myotonic dystrophy 1 (DM1) [MIM:160900]; also known as Steinert disease. DM1 is an autosomal dominant neurodegenerative disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness, and cardiac arrhythmias. DM1 patients show decreased levels of kinase expression inversely related to repeat length. The minimum estimated incidence is 1 in 8'000 live births. DM1 is caused by a CTG expansion in the 3'-UTR of the DMPK gene. The repeat length usually increases in successive generations, but not always.
Q9UI46	Defects in DNAI1 are the cause of primary ciliary dyskinesia type 1 (CILD1) [MIM:244400]. CILD1 is an autosomal recessive disorder characterized by axonemal abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit situs inversus, due to dysfunction of monocilia at the embryonic node and randomization of left-right body asymmetry. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.
Q9UI46	Defects in DNAI1 are the cause of Kartagener syndrome (KTGS) [MIM:244400]. KTGS is an autosomal recessive disorder characterized by the association of primary ciliary dyskinesia with situs inversus. Clinical features include recurrent respiratory infections, bronchiectasis, infertility, and lateral transposition of the viscera of the thorax and abdomen. The situs inversus is most often total, although it can be partial in some cases (isolated dextrocardia or isolated transposition of abdominal viscera).
Q9GZS0	Defects in DNAI2 are the cause of primary ciliary dyskinesia type 9 (CILD9) [MIM:612444]. CILD is an autosomal recessive disorder characterized by axonemal abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit situs inversus, due to dysfunction of monocilia at the embryonic node and randomization of left-right body asymmetry. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.
Q6VY05	Defects in Dnd1 are the cause of the Ter mutation phenotype. Ter mice are characterized by primordial germ cell loss and susceptibility to spontaneous testicular germ cell tumors (TGCT). They are sterile, but viable. Isoform 1 defects may be the cause of tumor development.
P49917	Defects in LIG4 are the cause of LIG4 syndrome [MIM:606593]. This disease is characterized by immunodeficiency and developmental and growth delay. Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and various skin abnormalities.
P49917	Defects in LIG4 are a cause of severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell- negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:602450]. SCID refers to a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients with SCID present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T-cell-mediated cellular immunity due to a defect in T- cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity.
Q9UBC3	Defects in DNMT3B are a cause of immunodeficiency- centromeric instability-facial anomalies syndrome (ICF) [MIM:242860]. ICF is a rare autosomal recessive disorder characterized by a variable immunodeficiency, mild facial anomalies, and centromeric heterochromatin instability involving chromosomes 1, 9, and 16. ICF is biochemically characterized by hypomethylation of CpG sites in some regions of heterochromatin.
P56542	Absence of Dnase2 is a cause of severe fetal anemia and of perinatal lethality due to malformation of the diaphragm.
Q8IZD9	A chromosomal aberration involving DOCK3 may be a cause of early-onset behavioral/developmental disorder with features of attention deficit-hyperactivity disorder and intellectual disability (ADHD) [MIM:143465]. Inversion inv(3)(p14:q21). The inversion disrupts DOCK3 and SLC9A9.
P59764	Defects in Dock4 are involved in the cause of some cancers, which are probably due to lack of Rap1 activation.
B2RY04	Defects in Dock5 are the cause of rupture of lens cataract. It affects both eyes and is inherited as an autosomal recessive trait. Homozygotes spontaneously develop opacity of the lens at 35-60 days of age. The initial pathological changes appear at about 35 days of age in the deep layer of the posterior cortex as irregular swelling, condensation, degeneration and fragmentation of the lens fibers, leading to rupture of the lens capsule at the posterior pole at 45-100 days of age. Following rupture, the lens nucleus becomes dislocated behind the lens or occasionally in the anterior chamber.
Q18PE1	Defects in DOK7 are the cause of familial limb-girdle myasthenia autosomal recessive (LGM) [MIM:254300]; also called congenital myasthenic syndrome type 1B or CMS1B. LGM is a congenital myasthenic syndrome characterized by a typical 'limb girdle' pattern of muscle weakness with small, simplified neuromuscular junctions but normal acetylcholine receptor and acetylcholinesterase function.
Q9UPQ8	Defects in DOLK are the cause of congenital disorder of glycosylation type 1M (CDG1M) [MIM:610768]; also known as dolichol kinase deficiency. CDGs are a family of severe inherited diseases caused by a defect in glycoprotein biosynthesis. They are characterized by under-glycosylated serum glycoproteins. These multisystem disorders present with a wide variety of clinical features, such as disorders of the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. CDG1M is a very severe disorder with death occurring in early infancy.
P09172	Defects in DBH are the cause of dopamine beta-hydroxylase deficiency (DBH deficiency) [MIM:223360]; also known as norepinephrine deficiency or noradrenaline deficiency. This disorder is characterized by profound deficits in autonomic and cardiovascular function, but apparently only subtle signs, if any, of central nervous system dysfunction.
Q8NEU8	A chromosomal aberration involving APPL2/DIP13B is a cause of the chromosome 22q13.3 deletion syndrome [MIM:606232]. Translocation t(12;22)(q24.1;q13.3) with SHANK3/PSAP2.
O60762	Defects in DPM1 are the cause of congenital disorder of glycosylation type 1E (CDG1E) [MIM:608799]. CDGs are metabolic deficiencies in glycoprotein biosynthesis that usually cause severe mental and psychomotor retardation. They are characterized by under-glycosylated serum glycoproteins. CDG1E is an autosomal recessive disorder, characterized by severe developmental delay, hypotnia, seizures, and dysmorphic features.
Q9P2X0	Defects in DPM3 are the cause of congenital disorder of glycosylation type 1O (CDG1O) [MIM:612937]. A multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
P54098	Defects in POLG are the cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 1 (PEOA1) [MIM:157640]. Progressive external ophthalmoplegia is characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged- red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.
P54098	Defects in POLG are a cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB) [MIM:258450]. PEOB is a severe form of progressive external ophthalmoplegia. It is clinically more heterogeneous than the autosomal dominant forms. Can be more severe.
P54098	Defects in POLG are a cause of sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) [MIM:607459]. SANDO is a clinically heterogeneous systemic disorder with variable features resulting from mitochondrial dysfunction. It shares phenotypic characteristics with autosomal recessive progressive external ophthalmoplegia and mitochondrial neurogastrointestinal encephalopathy syndrome. The clinical triad of symptoms consists of sensory ataxic, neuropathy, dysarthria, and ophthalmoparesis.
P54098	Defects in POLG are a cause of Alpers-Huttenlocher syndrome (AHS) [MIM:203700]; also called Alpers diffuse degeneration of cerebral gray matter with hepatic cirrhosis. AHS is an autosomal recessive hepatocerebral syndrome. The typical course of AHS includes severe developmental delay, intractable seizures, liver failure, and death in childhood. Refractory seizures, cortical blindness, progressive liver dysfunction, and acute liver failure after exposure to valproic acid are considered diagnostic features. The neuropathological hallmarks of AHS are neuronal loss, spongiform degeneration, and astrocytosis of the visual cortex. Liver biopsy results show steatosis, often progressing to cirrhosis.
P54098	Defects in POLG are a cause of mitochondrial neurogastrointestinal encephalopathy syndrome (MNGIE) [MIM:603041]; also known as myoneurogastrointestinal encephalomyopathy. MNGIE is an autosomal recessive disease associated with multiple deletions of skeletal muscle mitochondrial DNA (MtDNA). It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, thin body habitus, peripheral neuropathy, and myopathy.
P54098	Defects in POLG are a cause of Leigh syndrome (LS) [MIM:256000]. LS is a severe neurological disorder characterized by bilaterally symmetrical necrotic lesions in subcortical brain regions.
Q9UHN1	Defects in POLG2 are the cause of progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal dominant type 4 (PEOA4) [MIM:610131]. Progressive external ophthalmoplegia is characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged- red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism.
Q8N608	Genetic variations in DPP10 are associated with susceptibility to asthma (ASTHMA) [MIM:600807]. The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with weezing due to spasmodic contraction of the bronchi.
Q5T2R2	Defects in PDSS1 are a cause of coenzyme Q10 deficiency [MIM:607426]. Coenzyme Q10 deficiency is an autosomal recessive disorder with variable manifestations. It can be associated with three main clinical phenotypes: a predominantly myopathic form with central nervous system involvement, an infantile encephalomyopathy with renal dysfunction and an ataxic form with cerebellar atrophy.
Q96TH1	Defects in DPYD are the cause of dihydropyrimidine dehydrogenase deficiency (DPYD deficiency) [MIM:274270]; also known as hereditary thymine-uraciluria or familial pyrimidinemia. DPYD deficiency is a disease characterized by persistent urinary excretion of excessive amounts of uracil, thymine and 5- hydroxymethyluracil. Patients suffering from this disease show a severe reaction to the anticancer drug 5-fluorouracil. This reaction includes stomatitis, Leukopenia, thrombocytopenia, hair loss, diarrhea, fever, marked weight loss, cerebellar ataxia, and neurologic symptoms, progressing to semicoma.
Q14117	Defects in DPYS are the cause of DHP deficiency [MIM:222748]. DHP deficiency is an autosomal recessive disorder characterized by dihydropyrimidinuria and associated with a variable clinical phenotype: epileptic or convulsive attacks, dysmorphic features and severe developmental delay, and congenital microvillous atrophy.
P14416	Defects in DRD2 are associated with dystonia type 11 (DYT11) [MIM:159900]; also known as alcohol-responsive dystonia. DYT11 is a myoclonic dystonia. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT11 is characterized by involuntary lightning jerks and dystonic movements and postures alleviated by alcohol. Inheritance is autosomal dominant. The age of onset, pattern of body involvement, presence of myoclonus and response to alcohol are all variable.
P35462	Genetic variation in DRD3 may be associated with susceptibility to hereditary essential tremor 1 (ETM1) [MIM:190300]. ETM1 is the most common movement disorder. The main feature is postural tremor of the arms. Head, legs, trunk, voice, jaw, and facial muscles also may be involved. The condition can be aggravated by emotions, hunger, fatigue and temperature extremes, and may cause a functional disability or even incapacitation. Inheritance is autosomal dominant.
P21918	Defects in DRD5 are a cause of benign essential blepharospasm (BEB) [MIM:606798]. BEB is a primary focal dystonia affecting the orbicularis oculi muscles. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. BEB usually begins in middle age. Initial symptoms include eye irritation and frequent blinking, progressing to involuntary spasms of eyelid closure. Patients have normal eyes. The visual disturbance is due solely to the forced closure of the eyelids. In severe cases, this can lead to functional blindness.
Q02487	Defects in DSC2 are the cause of familial arrhythmogenic right ventricular dysplasia type 11 (ARVD11) [MIM:610476]; also known as arrhythmogenic right ventricular cardiomyopathy 11 (ARVC11). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall.
Q02413	Defects in DSG1 are the cause of palmoplantar keratoderma striate type 1 (SPPK1) [MIM:148700]; also known as keratosis palmoplantaris striata I. SPPK1 is a dermatoligical disorder characterized by thickening of the skin on the palms and soles, and longitudinal hyperkeratotic lesions on the palms, running the length of each finger.
Q14126	Defects in DSG2 are the cause of familial arrhythmogenic right ventricular dysplasia type 10 (ARVD10) [MIM:610193]; also known as arrhythmogenic right ventricular cardiomyopathy 10 (ARVC10). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall.
Q14126	Genetic variations in DSG2 are the cause of susceptibility to cardiomyopathy dilated type 1BB (CMD1BB) [MIM:612877]. A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Q86SJ6	Defects in DSG4 are the cause of hypotrichosis localized autosomal recessive type 1 (LAH1) [MIM:607903]. A condition characterized by the presence of less than the normal amount of hair, involving mainly the scalp, chest, arms and legs. It is characterized by abnormal hair follicles and shafts, which are thin and atrophic.
Q86SJ6	Autoantibodies against DSG4 are found in patients with pemphigus vulgaris. Pemphigus vulgaris is a potentially lethal skin disease in which epidermal blisters occur as the result of the loss of cell-cell adhesion.
Q7TMD7	Defects in Dsg4 are the cause of an autosomal recessive phenotype lanceolate hair (lah). Lah mice pups develop only a few short hairs on the head and neck which form a lance head at the tip and disappear within a few month. They have thickened skin and do not exhibit any growth retardation.
Q6W3B0	Defects in Dsg4 are the cause of an autosomal recessive phenotype lanceolate hair (lah). Lah rats pups develop only a few short hairs on the head and neck which form a lance head at the tip and disappear within one month. Hair regrows again a few days later, following a 29-day cycle of external growth and loss. Almost complete pelage hair loss occurs by 18 month.
Q9NZW4	Defects in DSPP are the cause of autosomal dominant deafness type 39 with dentinogenesis imperfecta 1 syndrome (DFNA39/DGI1) [MIM:605594]. Affected individuals present DGI1 associated with early onset progressive sensorineural high- frequency hearing loss.
Q9NZW4	Defects in DSPP are the cause of dentinogenesis imperfecta type 1 (DGI1) [MIM:125490]; also known as dentinogenesis imperfecta Shields type 2 (DGI2). DGI1 is an autosomal dominant disorder in which both the primary and the permanent teeth are affected. It occurs with an incidence of 1:8000 live births. The teeth are amber and opalescent, the pulp chamber being obliterated by abnormal dentin. The enamel, although unaffected, tends to fracture, which makes dentin undergo rapid attrition, leading to shortening of the teeth.
Q9NZW4	Defects in DSPP are a cause of dentinogenesis imperfecta Shields type 3 (DGI3) [MIM:125500]. Patients with DGI3 do not have stigmata of osteogenesis imperfecta [MIM:166240]. The finding that a single defects in the DSPP gene causes both phenotypic patterns of DGI2 and DGI3 strongly supports the conclusion that these two disorders are not separate diseases but rather the phenotypic variation of a single genetic defect.
Q9NZW4	Defects in DSPP are the cause of dentin dysplasia type 2 (DTDP2) [MIM:125420]; also known as dentin dysplasia Shields type 2. DTDP2 is an autosomal dominant disorder in which mineralization of the dentine of the primary teeth is abnormal. On the basis of the phenotypic overlap between, and shared chromosomal location with DGI2 it has been proposed that DTDP2 and DGI2 are allelic. From the results of recent studies, it is clear that different types of mutations in DSPP lead to the two different phenotypes.
P55265	Defects in ADAR are a cause of dyschromatosis symmetrical hereditaria (DSH) [MIM:127400]; also known as reticulate acropigmentation of Dohi. DSH is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal parts of the hands and feet.
Q96EV8	Defects in DTNBP1 are the cause of Hermansky-Pudlak syndrome type 7 (HPS7) [MIM:203300]. Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous, rare, autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS.
Q91WZ8	Defects in Dtnbp1 are the cause of the sandy (sdy) mutant phenotype, a model for human Hermansky-Pudlak syndrome (HPS). Sdy mice lack dysbindin expression; they have a characteristic sandy coat color and have much fewer melanosomes in the retinal pigment epithelium and choroid. They are fully viable, but present behavorial abnormalities. They have prolonged bleeding times due to platelet storage pool deficiency, and lysosomal storage defects. The number of electron-opaque platelet dense granules is severely reduced, and the platelet serotonin content is strongly reduced. Secretion of lysosomal enzymes from kidney and from thrombin-stimulated platelets is depressed 2- and 3-fold, and ceroid pigment is present in kidney.
Q13199	Defects in DTNA are the cause of non-compaction of left ventricular myocardium isolated autosomal dominant type 1 (LVNC1) [MIM:604169]. Left ventricular non-compaction (LVNC) is due to an arrest of myocardial morphogenesis. The disorder is characterized by a hypertrophic left ventricular with deep trabeculations and with poor systolic function, with or without associated left ventricular dilation. In some cases, the right ventricle is also affected.
Q13199	Defects in DTNA are a cause of non-compaction of left ventricular myocardium with congenital heart defects (LVNCCHD) [MIM:606617]; also known as non-isolated left ventricular non- compaction. LVNCCHD is associated with congenital heart anomalies such as ventricular septal defects, pulmonic stenosis, and atrial septal defects.
Q8R3P2	Recurrent site of retroviral integration in murine B-cell lymphomas.
Q9NRD8	Defects in DUOX2 are a cause of congenital hypothyroidism due to dyshormonogenesis type 6 (CHDH6) [MIM:607200]. CHDH6 is due to defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete.
Q9UBX2	Defects in DUX4 may be the cause of facioscapulohumeral muscular dystrophy (FSHD) [MIM:158900]. FSHD is characterized by weakness of the muscles of the face, upper-arm and shoulder girdle. Severity is highly variable. Weakness is slowly progressive and about 20% of affected individuals eventually require a wheelchair. Approximately 70-90% of individuals have inherited the disease-causing deletion from a parent, and approximately 10-30% of affected individuals have FSHD as the result of a de novo deletion. Offsprings of an affected individual have a 50% chance of inheriting the deletion.
Q96DT5	Defects in DNAH11 are a cause of Kartagener syndrome (KTGS) [MIM:244400]. KTGS is an autosomal recessive disorder characterized by the association of primary ciliary dyskinesia with situs inversus. Clinical features include recurrent respiratory infections, bronchiectasis, infertility, and lateral transposition of the viscera of the thorax and abdomen. The situs inversus is most often total, although it can be partial in some cases (isolated dextrocardia or isolated transposition of abdominal viscera).
Q96DT5	Defects in DNAH11 are the cause of primary ciliary dyskinesia type 7 (CILD7) [MIM:611884]. CILD is an autosomal recessive disorder characterized by axonemal abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit situs inversus, due to dysfunction of monocilia at the embryonic node and randomization of left-right body asymmetry. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.
Q8TE73	Defects in DNAH5 are the cause of primary ciliary dyskinesia type 3 (CILD3) [MIM:608644]. CILD3 is an autosomal recessive disorder characterized by axonemal abnormalities of motile cilia. Respiratory infections leading to chronic inflammation and bronchiectasis are recurrent, due to defects in the respiratory cilia; reduced fertility is often observed in male patients due to abnormalities of sperm tails. Half of the patients exhibit situs inversus, due to dysfunction of monocilia at the embryonic node and randomization of left-right body asymmetry. Primary ciliary dyskinesia associated with situs inversus is referred to as Kartagener syndrome.
Q8TE73	Defects in DNAH5 are a cause of Kartagener syndrome (KTGS) [MIM:244400]. KTGS is an autosomal recessive disorder characterized by the association of primary ciliary dyskinesia with situs inversus. Clinical features include recurrent respiratory infections, bronchiectasis, infertility, and lateral transposition of the viscera of the thorax and abdomen. The situs inversus is most often total, although it can be partial in some cases (isolated dextrocardia or isolated transposition of abdominal viscera).
Q8VHE6	Defects in Dnah5 are the cause of primary ciliary dyskinesia (PCD). PCD is characterized by recurrent respiratory infections, situs inversus and ciliary immotility and hydrocephalus.
Q9JHU4	Defects in Dync1h1 are the cause of the 'Legs at odd angles' (LOA) phenotype, an autosomal dominant trait where affected animals display unusual twisting of the body and clenching of the hindlimbs when suspended by the tail. Heterozygotes suffer age-related progressive loss of muscle tone and locomotor ability without major reduction in life-span while homozygotes show a more severe phenotype with an inability to move or feed, and die within 24 hours of birth. LOA mutants display defects in migration of facial motor neuron cell bodies and impaired retrograde transport in spinal cord motor neurons.
Q9JHU4	Defects in Dync1h1 are the cause of the Cramping 1 (Cra1) phenotype, an autosomal dominant trait where affected animals display unusual twisting of the body and clenching of the hindlimbs when suspended by the tail. Heterozygotes suffer age- related progressive loss of muscle tone and locomotor ability without major reduction in life-span while homozygotes show a more severe phenotype with an inability to move or feed, and die within 24 hours of birth.
Q9NPU7	Defects in DYM are the cause of Dyggve-Melchior-Clausen syndrome (DMC) [MIM:223800]. DMC is a rare autosomal recessive disorder characterized by short trunk dwarfism, microcephaly and psychomotor retardation. Electron microscopic study of cutaneous cells of affected patients shows dilated rough endoplasmic reticulum, enlarged and aberrant vacuoles and numerous vesicles. DMC is progressive.
Q9NPU7	Defects in DYM are the cause of Smith-McCort dysplasia (SMC) [MIM:607326]. SMC is a rare autosomal recessive osteochondrodysplasia characterized by short limbs and trunk with barrel-shaped chest. The radiographic phenotype includes platyspondyly, generalized abnormalities of the epiphyses and metaphyses, and a distinctive lacy appearance of the iliac crest, features identical to those of Dyggve-Melchior-Clausen syndrome.
P50570	Defects in DNM2 are a cause of centronuclear myopathy autosomal dominant (ADCNM) [MIM:160150]; also known as autosomal dominant myotubular myopathy. Centronuclear myopathies (CNMs) are congenital muscle disorders characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. CNMs comprise a wide spectrum of phenotypes, ranging from severe neonatal to mild late-onset familial forms. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.
P50570	Defects in DNM2 are the cause of Charcot-Marie-Tooth disease dominant intermediate type B (CMTDIB) [MIM:606482]. Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. CMTDIB is a form of Charcot-Marie-Tooth disease characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
Q0H395	Defects in DYSF are the cause of limb-girdle muscular dystrophy type 2B (LGMD2B) [MIM:253601]. LGMD2B is an autosomal recessive degenerative myopathy characterized by weakness and atrophy starting in the proximal pelvifemoral muscles, with onset in the late teens or later, massive elevation of serum creatine kinase levels and slow progression. Scapular muscle involvement is minor and not present at onset. Upper limb girdle involvement follows some years after the onset in lower limbs.
Q0H395	Defects in DYSF are the cause of Miyoshi myopathy (MM) [MIM:254130]. This type of autosomal recessive muscular dystrophy involves the distal lower limb musculature. It is characterized by weakness that initially affects the gastrocnemius muscle during early adulthood. Otherwise the phenotype overlaps with LGMD2B, especially in age at onset and creatine kinase elevation.
Q0H395	Defects in DYSF are the cause of distal myopathy with anterior tibial onset (DMAT) [MIM:606768]. Onset of the disorder is between 14 and 28 years of age and the anterior tibial muscles are the first muscle group to be involved. Inheritance is autosomal recessive.
Q9ESD7	Defects in Dysf are the cause of a slowly progressive muscular dystrophy observed in SJL mice. It affects primarily the proximal muscles and it is inherited as autosomal recessive trait.
Q8WXU2	A chromosomal aberration involving DYX1C1 may be a cause of dyslexia [MIM:127700]. Translocation t(2;15)(q11;q21).
Q9Z2R9	Defects in Eif2ak1 are a cause of hyperchromic anemia in animals suffering from iron deficiency. The number of red blood cells is decreased due to increased apoptosis of erythroid precursor cells, probably because globins misfold and aggregate in the absence of heme.
Q9NZJ5	Defects in EIF2AK3 are the cause of Wolcott-Rallison syndrome (WRS) [MIM:226980]; also known as multiple epiphyseal dysplasia with early-onset diabetes mellitus. WRS is a rare autosomal recessive disorder, characterized by permanent neonatal or early infancy insulin-dependent diabetes and, at a later age, epiphyseal dysplasia, osteoporosis, growth retardation and other multisystem manifestations, such as hepatic and renal dysfunctions, mental retardation and cardiovascular abnormalities.
P43003	Defects in SLC1A3 are the cause of episodic ataxia type 6 (EA6) [MIM:612656]. EA6 is characterized by episodic ataxia, seizures, migraine and alternating hemiplegia.
P43005	Defects in SLC1A1 may be a cause of dicarboxylicamino aciduria [MIM:222730]; also known as glutamate-aspartate transport defect. This is as defect in renal and probably intestinal transport of glutamic and aspartic acids and is associated with moderate hyperprolinemia.
Q15125	Defects in EBP are the cause of chondrodysplasia punctata X-linked dominant type 2 (CDPX2) [MIM:302960]; also known as Conradi-Hunermann-Happle syndrome. CDP is a clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. The key clinical features of CDPX2 are chondrodysplasia punctata, linear ichthyosis, cataracts and short stature. CDPX2 is a rare disorder of defective cholesterol biosynthesis, biochemically characterized by an increased amount of 8-dehydrocholesterol and cholest-8(9)-en-3-beta-ol in the plasma and tissues.
P70245	Defects in Ebp are a cause of 'Tattered' (Td) which is an X-linked, semidominant mouse mutation associated with prenatal male lethality. Heterozygous females are small and at 4 to 5 days of age develop patches of hyperkeratotic skin where no hair grows, resulting in a striping of the coat in adults. Craniofacial anomalies and twisted toes have also been observed in some affected females.
Q5THM8	Defects in ECE1 are a cause of Hirschsprung disease, cardiac defects and autonomic dysfunction [MIM:600423]. It is a form of Hirschsprung disease [MIM:142623] with skip-lesions defects, craniofacial abnormalities and other dysmorphic features, and autonomic dysfunction.
P40939	Defects in HADHA are a cause of trifunctional protein deficiency (TFP deficiency) [MIM:609015]. The clinical manifestations are very variable and include hypoglycemia, cardiomyopathy and sudden death. Phenotypes with mainly hepatic and neuromyopathic involvement can also be distinguished. Biochemically, TFP deficiency is defined by the loss of all enzyme activities of the TFP complex.
P40939	Defects in HADHA are the cause of long-chain 3-hydroxyl- CoA dehydrogenase deficiency (LCHAD deficiency) [MIM:609016]. The clinical features are very similar to TFP deficiency. Biochemically, LCHAD deficiency is characterized by reduced long- chain 3-hydroxyl-CoA dehydrogenase activity, while the other enzyme activities of the TFP complex are normal or only slightly reduced.
P40939	Defects in HADHA are a cause of maternal acute fatty liver of pregnancy (AFLP) [MIM:609016]. AFLP is a severe maternal illness occurring during pregnancies with affected fetuses. This disease is associated with LCHAD deficiency and characterized by sudden unexplained infant death or hypoglycemia and abnormal liver enzymes (Reye-like syndrome).
P55084	Defects in HADHB are a cause of trifunctional protein deficiency (TFP deficiency) [MIM:609015]. The clinical manifestations are very variable and include hypoglycemia, cardiomyopathy and sudden death. Phenotypes with mainly hepatic and neuromyopathic involvement can also be distinguished. Biochemically, TFP deficiency is defined by the loss of all three enzyme activities of the TFP complex.
Q8IZ60	Defects in ECM1 are the cause of lipoid proteinosis (LiP) [MIM:247100]; also known as lipoid proteinosis of Urbach and Wiethe or hyalinosis cutis et mucosae. LiP is a rare autosomal recessive disorder characterized by generalized thickening of skin, mucosae and certain viscera. Classical features include beaded eyelid papules and laryngeal infiltration leading to hoarseness. Histologically, there is widespread deposition of hyaline material and disruption/reduplication of basement membrane.
Q8WWZ3	Defects in EDARADD are a cause of ectodermal dysplasia anhidrotic (EDA) [MIM:224900]; also known ectodermal dysplasia hypohidrotic autosomal recessive (HED). Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDA is characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands.
Q9UNE0	Defects in EDAR are a cause of ectodermal dysplasia anhidrotic (EDA) [MIM:224900]; also known ectodermal dysplasia hypohidrotic autosomal recessive (HED). Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDA is characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands.
Q9UNE0	Defects in EDAR are the cause of ectodermal dysplasia type 3 (ED3) [MIM:129490]; also known as ectodermal dysplasia hypohidrotic autosomal dominant or EDA3. ED3 is an autosomal dominant condition characterized by hypotrichosis, abnormal or missing teeth, and hypohidrosis due to the absence of sweat glands.
Q9R187	Defects in Edar are a cause of the downless phenotype in mice (the equivalent of anhidrotic ectodermal dysplasia in humans). The disease is characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands.
Q9BEG5	Defects in EDA are the cause of anhidrotic ectodermal dysplasia. The disease is characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands.
Q9UP77	Defects in EDA are the cause of ectodermal dysplasia type 1 (ED1) [MIM:305100]; also known as Christ-Siemens-Touraine syndrome or X-linked hypohidrotic ectodermal dysplasia (XLHED). Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. ED1 is a disease characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands. ED1 is the most common form of over 150 clinically distinct ectodermal dysplasias.
Q9UP77	Defects in EDA are a cause of hypodontia [MIM:300606]. Hypodontia is agenesis of two or more permanent teeth without associated systemic disorders. Hypodontia due to EDA defects is an X-linked recessive disorder. Affected individuals have normal hair, skin, and nails, but lack primary and permanent teeth.
O54693	Defects in Eda are the cause of the tabby phenotype in mice (the equivalent of anhidrotic ectodermal dysplasia in humans). The disease is characterized by sparse hair (atrichosis or hypotrichosis), abnormal or missing teeth and the inability to sweat due to the absence of sweat glands.
P14138	Defects in EDN3 are the cause of Hirschsprung disease type 1 (HSCR1) [MIM:142623]; also known as aganglionic megacolon (MGC). HSCR1 is a genetic disorder of neural crest development characterized by the absence of intramural ganglion cells in the hindgut; often resulting in intestinal obstruction.
P14138	Defects in EDN3 are a cause of congenital central hypoventilation syndrome (CCHS) [MIM:209880]; also known as congenital failure of autonomic control or Ondine curse. CCHS is a rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia.
P14138	Defects in EDN3 are a cause of Waardenburg syndrome type 4 (WS4) [MIM:277580]; also known as Waardenburg-Shah syndrome. WS4 is characterized by the association of Waardenburg features (depigmentation and deafness) and the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease).
O62709	Defects in EDNRB are a cause of overo lethal white syndrome (OLWS) also known as lethal white foal syndrome (LWFS). It is an inherited syndrome of foals born to American paint horse parents of the overo coat-pattern lineage. Affected foals are totally or almost totally white and die within days from complications due to intestinal aganglionosis.
Q8NHM8	Defects in EDNRB are a cause of Waardenburg syndrome type 4 (WS4) [MIM:277580]; also known as Waardenburg-Shah syndrome. WS4 is characterized by the association of Waardenburg features (depigmentation and deafness) and the absence of enteric ganglia in the distal part of the intestine (Hirschsprung disease).
Q8NHM8	Defects in EDNRB are the cause of Hirschsprung disease type 2 (HSCR2) [MIM:600155]; also known as aganglionic megacolon (MGC). HSCR2 is a congenital disorder characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child.
Q8NHM8	Defects in EDNRB are the cause of ABCD syndrome (ABCDS) [MIM:600501]. ABCD syndrome is an autosomal recessive syndrome characterized by albinism, black lock at temporal occipital region, bilateral deafness, aganglionosis of the large intestine and total absence of neurocytes and nerve fibers in the small intestine.
Q96RP9	Defects in GFM1 are the cause of combined oxidative phosphorylation deficiency type 1 (COXPD1) [MIM:609060]. It leads to early fatal progressive hepatoencephalopathy.
Q5JVL4	Defects in EFHC1 are the cause of juvenile myoclonic epilepsy type 1 (EJM1) [MIM:254770]. EJM1 is a subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue.
Q5JVL4	Genetic variations in EFHC1 are the cause of susceptibility to juvenile absence epilepsy type 1 (JAE1) [MIM:607631]. JAE is a subtype of idiopathic generalized epilepsy characterized by onset occurring around puberty, absence seizures, generalized tonic-clonic seizures (GTCS), GTCS on awakening, and myoclonic seizures.
P98172	Defects in EFNB1 are a cause of craniofrontonasal syndrome (CFNS) [MIM:304110]; also known as craniofrontonasal dysplasia (CFND). CFNS is an X-linked inherited syndrome characterized by hypertelorism, coronal synostosis with brachycephaly, downslanting palpebral fissures, clefting of the nasal tip, joint anomalies, longitudinally grooved fingernails and other digital anomalies.
P43897	Defects in TSFM are the cause of combined oxidative phosphorylation deficiency type 3 (COXPD3) [MIM:610505]. Defects in the mitochondrial oxidative phosphorylation system result in devastating, mainly multisystem, diseases. COXPD3 symptoms include severe metabolic acidosis with encephalomyopathy or with hypertrophic cardiomyopathy. Patients show a severe defect in mitochondrial translation leading to a failure to assemble adequate amounts of three of the oxidative phosphorylation complexes.
P49411	Defects in TUFM are the cause of combined oxidative phosphorylation deficiency type 4 (COXPD4) [MIM:610678]. COXPD4 is characterized by neonatal lactic acidosis, rapidly progressive encephalopathy, severely decreased mitochondrial protein synthesis, and combined deficiency of mtDNA-related mitochondrial respiratory chain complexes.
Q9GZX1	Defects in EGFR are associated with lung cancer [MIM:211980].
P01133	Defects in EGF are the cause of hypomagnesemia type 4 (HOMG4) [MIM:611718]; also known as renal hypomagnesemia normocalciuric. HOMG4 is a disorder characterized by massive renal hypomagnesemia and normal levels of serum calcium and calcium excretion. Clinical features include seizures, mild-to mederate psychomotor retardation, and brisk tendon reflexes.
Q9GZT9	Defects in EGLN1 are the cause of erythrocytosis familial type 3 (ECYT3) [MIM:609820]. ECYT3 is an autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels.
P17813	Defects in ENG are the cause of hereditary hemorrhagic telangiectasia type 1 (HHT1) [MIM:187300, 108010]; also known as Osler-Rendu-Weber syndrome 1 (ORW1). HHT1 is an autosomal dominant multisystemic vascular dysplasia, characterized by recurrent epistaxis, muco-cutaneous telangiectases, gastro-intestinal hemorrhage, and pulmonary (PAVM), cerebral (CAVM) and hepatic arteriovenous malformations; all secondary manifestations of the underlying vascular dysplasia. Although the first symptom of HHT1 in children is generally nose bleed, there is an important clinical heterogeneity.
P11161	Defects in EGR2 are a cause of congenital hypomyelination neuropathy (CHN) [MIM:605253]. Inheritance can be autosomal dominant or recessive. Recessive CHN is also known as Charcot- Marie-Tooth disease type 4E (CMT4E). CHN is characterized clinically by early onset of hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities.
P11161	Defects in EGR2 are a cause of Charcot-Marie-Tooth disease type 1D (CMT1D) [MIM:607678]. CMT1D is a form of Charcot- Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy or CMT1, and primary peripheral axonal neuropathy or CMT2. Neuropathies of the CMT1 group are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet.
P11161	Defects in EGR2 are a cause of Dejerine-Sottas syndrome (DSS) [MIM:145900]; also known as Dejerine-Sottas neuropathy (DSN) or hereditary motor and sensory neuropathy III (HMSN3). DSS is a severe degenerating neuropathy of the demyelinating Charcot-Marie- Tooth disease category, with onset by age 2 years. DSS is characterized by motor and sensory neuropathy with very slow nerve conduction velocities, increased cerebrospinal fluid protein concentrations, hypertrophic nerve changes, delayed age of walking as well as areflexia. There are both autosomal dominant and autosomal recessive forms of Dejerine-Sottas syndrome.
Q9NWI9	A genetic variation in EHBP1 is associated with susceptibility to hereditary prostate cancer type 12 (HPC12) [MIM:611868].
Q9H9B1	Defects in EHMT1 are the cause of chromosome 9q subtelomeric deletion syndrome (9q- syndrome) [MIM:610253]. Common features seen in these patients are severe mental retardation, hypotonia, brachy(micro)cephaly, epileptic seizures, flat face with hypertelorism, synophrys, anteverted nares, cupid bow or tented upper lip, everted lower lip, prognathism, macroglossia, conotruncal heart defects, and behavioral problems.
Q14232	Defects in EIF2B1 are a cause of leukodystrophy with vanishing white matter (VWM) [MIM:603896]. VWM is a leukodystrophy that occurs mainly in children. Neurological signs include progressive cerebellar ataxia, spasticity, inconstant optic atrophy and relatively preserved mental abilities. The disease is chronic-progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. While childhood onset is the most common form of the disorder, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood. Some females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy.
P49770	Defects in EIF2B2 are a cause of leukodystrophy with vanishing white matter (VWM) [MIM:603896]. VWM is a leukodystrophy that occurs mainly in children. Neurological signs include progressive cerebellar ataxia, spasticity, inconstant optic atrophy and relatively preserved mental abilities. The disease is chronic-progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. While childhood onset is the most common form of the disorder, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood. Some females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy.
Q9UI10	Defects in EIF2B4 are a cause of leukodystrophy with vanishing white matter (VWM) [MIM:603896]. VWM is a leukodystrophy that occurs mainly in children. Neurological signs include progressive cerebellar ataxia, spasticity, inconstant optic atrophy and relatively preserved mental abilities. The disease is chronic-progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. While childhood onset is the most common form of the disorder, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood. Some females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy.
Q13144	Defects in EIF2B5 are a cause of leukodystrophy with vanishing white matter (VWM) [MIM:603896]. VWM is a leukodystrophy that occurs mainly in children. Neurological signs include progressive cerebellar ataxia, spasticity, inconstant optic atrophy and relatively preserved mental abilities. The disease is chronic-progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. While childhood onset is the most common form of the disorder, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood. Some females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy.
Q9NR50	Defects in EIF2B3 are a cause of leukodystrophy with vanishing white matter (VWM) [MIM:603896]. VWM is a leukodystrophy that occurs mainly in children. Neurological signs include progressive cerebellar ataxia, spasticity, inconstant optic atrophy and relatively preserved mental abilities. The disease is chronic-progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. While childhood onset is the most common form of the disorder, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood. Some females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy.
P60229	Int-6 serves as a site for viral integration of mouse mammary tumor virus (MMTV) in mammary tumors.
P55199	A chromosomal aberration involving ELL is found in acute leukemias. Translocation t(11;19)(q23;p13.1) with MLL/HRX. The result is a rogue activator protein.
P08246	Defects in ELANE are a cause of cyclic haematopoiesis (CH) [MIM:162800]; also known as cyclic neutropenia. CH is an autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency.
P08246	Defects in ELANE are the cause of autosomal dominant severe congenital neutropenia type 1 (SCN1) [MIM:202700]. SCN is a heterogeneous disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.
Q6ZWJ6	Defects in ELN are a cause of autosomal dominant cutis laxa [MIM:123700]. Cutis laxa is a rare connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. The skin changes are often accompanied by extracutaneous manifestations, including pulmonary emphysema, bladder diverticula, pulmonary artery stenosis and pyloric stenosis.
Q6ZWJ6	Haploinsufficiency of ELN may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in Williams-Beuren syndrome (WBS) [MIM:194050]. WBS is a rare developmental disorder and a contiguous gene deletion syndrome involving genes from chromosome band 7q11.23.
Q6ZWJ6	Defects in ELN are the cause of supravalvular aortic stenosis (SVAS) [MIM:185500]. SVAS is a congenital narrowing of the ascending aorta which can occur sporadically, as an autosomal dominant condition, or as one component of Williams-Beuren syndrome.
Q9GZR5	Defects in ELOVL4 are the cause of Stargardt disease type 3 (STGD3) [MIM:600110]. STGD is one of the most frequent causes of macular degeneration in childhood. It is characterized by macular dystrophy with juvenile-onset, rapidly progressive course, alterations of the peripheral retina, and subretinal deposition of lipofuscin-like material. STGD3 inheritance is autosomal dominant.
O95163	Defects in IKBKAP are the cause of familial dysautonomia (FD) [MIM:223900]; also known as Riley-Day syndrome or hereditary sensory and autonomic neuropathy type III. This autosomal recessive disorder is due to the poor development and survival, and progressive degeneration of the sensory, sympathetic and parasympathetic neurons. FD individuals are affected with a variety of symptoms such as decreased sensitivity to pain and temperature, cardiovascular instability, recurrent pneumonias, vomiting crises, and gastrointestinal dysfunction. It is primarily confined to individuals of Ashkenazi Jewish descent, with an incidence of 1/3600 live births.
P50402	Defects in EMD are a cause of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) [MIM:310300]. X-EDMD is an X-linked disorder characterized by early contractures, muscle wasting and weakness and cardiomyopathy.
Q04743	Defects in EMX2 are the cause of schizencephaly [MIM:269160]. Schizencephaly is an extremely rare human congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. These clefts are lined with gray matter and most commonly involve the parasylvian regions. Large portions of the cerebral hemispheres may be absent and replaced by cerebro- spinal fluid.
Q9NRM1	Defects in ENAM are the cause of amelogenesis imperfecta hypoplastic type 1B (AI1B) [MIM:104500]. AI1B is an autosomal dominant defect of enamel formation. Clinical manifestations may be variable. Some cases present with generalized enamel hypoplasia resulting in small, smooth, yellow and spaced teeth (smooth hypoplastic AI). Others show horizontal rows of pits, grooves or a hypoplastic area in the enamel (local hypoplastic AI).
Q9NRM1	Defects in ENAM are the cause of amelogenesis imperfecta type 1C (AI1C) [MIM:204650]; also known as amelogenesis imperfecta hypoplastic with or without openbite malocclusion. AI1C is an autosomal recessive defect of dental enamel formation. Teeth show hypoplastic and unmineralized enamel, and a yellow-brown discoloration. Enamel defects can be associated with facial and oral features including vertical dysgnathia and anterior openbite malocclusion.
Q03111	A chromosomal aberration involving MLLT1 is associated with acute leukemias. Translocation t(11;19)(q23;p13.3) with MLL/HRX. The result is a rogue activator protein.
P13929	Defects in ENO3 are the cause of glycogen storage disease type 13 (GSD13) [MIM:612932]. A metabolic disorder that results in exercise-induced myalgias, generalized muscle weakness and fatigability. It is characterized by increased serum creatine kinase and decreased enolase 3 activity. Dramatically reduced protein levels with focal sarcoplasmic accumulation of glycogen- beta particles are detected on ultrastructural analysis.
P22413	Defects in ENPP1 are a cause of increased susceptibility for ossification of the posterior longitudinal ligament of the spine (OPLL) [MIM:602475]. OPLL is a common form of human myelopathy with a prevalence of as much as 4% in a variety of ethnic groups.
P22413	Defects in ENPP1 are a cause of idiopathic infantile arterial calcification (IIAC) [MIM:208000]; also known as generalized arterial calcification of infancy. IIAC is characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation.
P22413	Defects in ENPP1 are associated with obesity, glucose intolerance, and type II diabetes non-insulin dependent (NIDDM) [MIM:125853].
P06802	Defects in Enpp1 are the cause of the tiptoe walking (ttw) phenotype. Ttw mice exhibit ossification of the spinal ligaments.
Q9R1E6	May contribute to obesity.
P98073	Defects in PRSS7 are a cause of enterokinase deficiency [MIM:226200]; a life-threatening intestinal malabsorption disorder characterized by diarrhea and failure to thrive.
Q9QYC8	ENTPD5 has transforming capacity and tumorigenic Potential.
Q09472	Defects in EP300 may play a role in epithelial cancer.
Q09472	Chromosomal aberrations involving EP300 may be a cause of acute myeloid leukemias. Translocation t(8;22)(p11;q13) with MYST3.
Q09472	Defects in EP300 are a cause of Rubinstein-Taybi syndrome (RSTS) [MIM:180849]. RSTS is an autosomal dominant disorder characterized by craniofacial abnormalities, broad thumbs, broad big toes, mental retardation and a propensity for development of malignancies.
Q99814	Defects in EPAS1 are the cause of erythrocytosis familial type 4 (ECYT4) [MIM:611783]. ECYT4 is an autosomal dominant disorder characterized by increased serum red blood cell mass, elevated hemoglobin concentration and hematocrit, and normal platelet and leukocyte counts.
P16452	Defects in EPB42 are the cause of spherocytosis type 5 (SPH5) [MIM:612690]; also known as hereditary spherocytosis type 5 (HS5). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Absence of band 4.2 associated with spur or target erythrocytes has also been reported.
P29317	Genetic variations in EPHA2 are the cause of susceptibility to cataract cortical age-related type 2 (ARCC2) [MIM:613020]. A developmental punctate opacity common in the cortex and present in most lenses. The cataract is white or cerulean, increases in number with age, but rarely affects vision.
P29317	Defects in EPHA2 are the cause of cataract posterior polar type 1 (CTPP1) [MIM:116600]. A subcapsular opacity, usually disk-shaped, located at the back of the lens. It can have a marked effect on visual acuity.
P29320	Defects in EPHA3 may be a cause of colorectal cancer (CRC) [MIM:114500].
P29323	Defects in EPHB2 are involved in the progression of prostate cancer [MIM:176807].
P29323	Defects in EPHB2 are involved in the development of prostate cancer metastasis to the brain [MIM:603688].
O95278	Defects in EPM2A are a cause of progressive myoclonic epilepsy type 2 (EPM2) [MIM:254780]; also known as Lafora disease. EPM2 is an autosomal recessive and severe form of adolescent-onset progressive epilepsy. Typically, as seizures increase in frequency, cognitive function declines towards dementia, and affected individuals die usually within 10 years after onset. EPM2 occurs worldwide, but it is particularly common in the mediterranean countries of southern Europe and northern Africa, in southern India and in the Middle East. At the cellular level, it is characterized by accumulation of starch-like polyglucosans called Lafora bodies (LBs) that are most abundant in organs with the highest glucose metabolism: brain, heart, liver and skeletal muscle. Among other conditions involving polyglucosans, EPM2 is unique in that the inclusions are in neuronal dendrites but not axons and the forming polyglucosan fibrils are associated with the endoplasmic reticulum.
P19235	Defects in EPOR are the cause of erythrocytosis familial type 1 (ECYT1) [MIM:133100]. ECYT1 is an autosomal dominant disorder characterized by increased serum red blood cell mass, elevated hemoglobin and hematocrit, hypersensitivity of erythroid progenitors to erythropoietin, erythropoietin low serum levels, and no increase in platelets nor leukocytes. It has a relatively benign course and does not progress to leukemia.
P01588	Genetic variation in EPO is associated with susceptbility to microvascular complications of diabetes type 2 (MVCD2) [MIM:612623]; also called susceptibility to proliferative diabetic retinopathy (PDR) or susceptbility to diabetic end-stage renal disease (ESRD). Significant morbidity and mortality among patients with diabetes mellitus result largely from a greatly increased incidence of microvascular complications. PDR and ESRD are two of the most common and severe microvascular complications of diabetes. A high concordance exists in the development of PDR and ESRD in diabetic patients, as well as strong familial aggregation of these complications, suggesting a common underlying genetic mechanism. EPO is a potent angiogenic factor observed in the diabetic human and mouse eye.
P42566	A chromosomal aberration involving EPS15 is found in acute leukemias. Translocation t(1;11)(p32;q23) with MLL/HRX. The result is a rogue activator protein.
P04626	Defects in ERBB2 are associated with gastric cancer [MIM:137215]; also known as hereditary familial diffuse gastric cancer (HDGC).
P04626	Defects in ERBB2 are associated with familial glioma of brain [MIM:137800]; also called glioblastoma multiforme. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas.
P04626	Defects in ERBB2 are associated with ovarian cancer [MIM:167000]. Ovarian cancer is the leading cause of death from gynecologic malignancy. It is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases. These typical features relate to the biology of the disease, which is a principal determinant of outcome.
P04626	Defects in ERBB2 are associated with lung cancer [MIM:211980]; also called adenocarcinoma of lung.
P21860	Defects in ERBB3 are the cause of lethal congenital contracture syndrome type 2 (LCCS2) [MIM:607598]; also called Israeli Bedouin multiple contracture syndrome type A. LCCS2 is an autosomal recessive neurogenic form of a neonatally lethal arthrogryposis that is associated with atrophy of the anterior horn of the spinal cord. The LCCS2 syndrome is characterized by multiple joint contractures, anterior horn atrophy in the spinal cord, and a unique feature of a markedly distended urinary bladder. The phenotype suggests a spinal cord neuropathic etiology.
P07992	Defects in ERCC1 are the cause of cerebro-oculo-facio- skeletal syndrome type 4 (COFS4) [MIM:610758]. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur.
P18074	Defects in ERCC2 are the cause of xeroderma pigmentosum complementation group D (XP-D) [MIM:278730]; also known as XP group D (XPD). Xeroderma pigmentosum is an autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Some XP-D patients present features of Cockayne syndrome, including dwarfism, sensorineural deafness, microcephaly, mental retardation, pigmentary retinopathy, ataxia, decreased nerve conduction velocities.
P18074	Defects in ERCC2 are a cause of trichothiodystrophy photosensitive (TTDP) [MIM:601675]. TTDP is an autosomal recessive disease characterized by sulfur-deficient brittle hair and nails, ichthyosis, mental retardation, impaired sexual development, abnormal facies and cutaneous photosensitivity correlated with a nucleotide excision repair (NER) defect. Neonates with trichothiodystrophy and ichthyosis are usually born with a collodion membrane. The severity of the ichthyosis after the membrane is shed is variable, ranging from a mild to severe lamellar ichthyotic phenotype. There are no reports of skin cancer associated with TTDP.
P18074	Defects in ERCC2 are the cause of cerebro-oculo-facio- skeletal syndrome type 2 (COFS2) [MIM:610756]. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur.
P19447	Defects in ERCC3 are the cause of xeroderma pigmentosum complementation group B (XP-B) [MIM:610651]; also known as xeroderma pigmentosum II (XP2) or XP group B (XPB) or xeroderma pigmentosum group B combined with Cockayne syndrome (XP-B/CS). Xeroderma pigmentosum is an autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Some XP-B patients present features of Cockayne syndrome, including dwarfism, sensorineural deafness, microcephaly, mental retardation, pigmentary retinopathy, ataxia, decreased nerve conduction velocities.
P19447	Defects in ERCC3 are a cause of trichothiodystrophy photosensitive (TTDP) [MIM:601675]. TTDP is an autosomal recessive disease characterized by sulfur-deficient brittle hair and nails, ichthyosis, mental retardation, impaired sexual development, abnormal facies and cutaneous photosensitivity correlated with a nucleotide excision repair (NER) defect. Neonates with trichothiodystrophy and ichthyosis are usually born with a collodion membrane. The severity of the ichthyosis after the membrane is shed is variable, ranging from a mild to severe lamellar ichthyotic phenotype. There are no reports of skin cancer associated with TTDP.
P28715	Defects in ERCC5 are the cause of xeroderma pigmentosum complementation group G (XP-G) [MIM:278780]; also known as xeroderma pigmentosum VII (XP7). Xeroderma pigmentosum is an autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. Some XP-G patients present features of Cockayne syndrome, including dwarfism, sensorineural deafness, microcephaly, mental retardation, pigmentary retinopathy, ataxia, decreased nerve conduction velocities.
Q03468	Defects in ERCC6 are the cause of Cockayne syndrome type B (CSB) [MIM:133540]. Cockayne syndrome is a rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer.
Q03468	Defects in ERCC6 are the cause of cerebro-oculo-facio- skeletal syndrome type 1 (COFS1) [MIM:214150]; also known as COFS syndrome or Pena-Shokeir syndrome type 2. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur.
Q03468	Defects in ERCC6 are a cause of De Sanctis-Cacchione syndrome (DSC) [MIM:278800]; also known as xerodermic idiocy. DSC is an autosomal recessive syndrome consisting of xeroderma pigmentosum associated with mental retardation, retarded growth, gonadal hypoplasia and sometimes neurologic complications.
Q03468	Genetic variation in ERCC6 is associated with susceptibility to age-related macular degeneration type 5 (ARMD5) [MIM:609413]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
Q03468	Defects in ERCC6 are a cause of UV-sensitive syndrome (UVS) [MIM:600630]. UVS is a rare autosomal recessive disorder characterized by photosensitivity and mild freckling but without neurological abnormalities or skin tumors.
Q13216	Defects in ERCC8 are the cause of Cockayne syndrome type A (CSA) [MIM:216400]. Cockayne syndrome is a rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer.
P11308	A chromosomal aberration involving ERG is a cause of Erwing sarcoma [MIM:133450]. Translocation t(21;22)(q22;q12) with ERW.
P11308	A chromosomal aberration involving ERG is a cause of acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with FUS.
O95718	Defects in ESRRB are the cause of non-syndromic sensorineural deafness autosomal recessive type 35 (DFNB35) [MIM:608565]. DFNB35 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
Q56NI9	Defects in ESCO2 are the cause of Roberts syndrome (RBS) [MIM:268300]. RBS is a rare autosomal recessive disorder characterized by pre- and postnatal growth retardation, microcephaly, bilateral cleft lip and palate, and mesomelic symmetric limb reduction. Severely affected infants may be stillborn or die shortly after birth. RBS chromosomes have a lack of cohesion involving the heterochromatic C-banding regions around centromeres and the distal portion of the long arm of the Y chromosome (known as premature centromere separation, heterochromatin repulsion or puffing, or RS effect).
Q56NI9	Defects in ESCO2 are the cause of SC phocomelia syndrome [MIM:269000]; also known as SC pseudothalidomide syndrome. SC phocomelia syndrome has a milder phenotype than RBS, with a lesser degree of symmetric limb reduction and additionally includes flexion contractures of various joints, midfacial hemangioma, hypoplastic cartilage of ears and nose, scant silvery-blond hair, and cloudy corneae. Although microcephaly is present, mental retardation may be mild and survival into adulthood is common.
B1AK53	Defects in ESPN are the cause of non-syndromic sensorineural deafness autosomal recessive type 36 (DFNB36) [MIM:609006]. DFNB36 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB36 is characterized by prelingual, profound hearing loss and vestibular areflexia.
B1AK53	Defects in ESPN are the cause of non-syndromic sensorineural deafness autosomal dominant without vestibular involvement (DFNAWVI) [MIM:606351].
P13804	Defects in ETFA are the cause of glutaric aciduria type 2A (GA2A) [MIM:231680]; also known as glutaricaciduria IIA. GA2A is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.
P38117	Defects in ETFB are the cause of glutaric aciduria type 2B (GA2B) [MIM:231680]. GA2B is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.
Q16134	Defects in ETFDH are the cause of glutaric aciduria type 2C (GA2C) [MIM:231680]. GA2C is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It is characterized by multiple acyl-CoA dehydrogenase deficiencies resulting in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.
O95571	Defects in ETHE1 are a cause of ethylmalonic encephalopathy (EE) [MIM:602473]. EE is an autosomal recessive disorder characterized by neurodevelopmental delay and regression, recurrent petechiae, acrocyanosis, diarrhea, leading to death in the first decade of life. It is also associated with persistent lactic acidemia and ethylmalonic and methylsuccinic aciduria.
P50549	A chromosomal aberration involving ETV1 is a cause of Ewing sarcoma [MIM:133450]. Translocation t(7;22)(p22;q12) with EWS.
P41212	A chromosomal aberration involving ETV6 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;12)(q33;p13) with PDGFRB. It is characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML).
P41212	Chromosomal aberrations involving ETV6 are found in a form of acute myeloid leukemia (AML). Translocation t(12;22)(p13;q11) with MN1; translocation t(4;12)(q12;p13) with CHIC2.
P41212	Chromosomal aberrations involving ETV6 are found in childhood acute lymphoblastic leukemia (ALL). Translocations t(12;21)(p12;q22) and t(12;21)(p13;q22) with RUNX1/AML1.
P41212	A chromosomal aberration involving ETV6 is found in a form of pre-B acute myeloid leukemia. Translocation t(9;12)(p24;p13) with JAK2.
P41212	A chromosomal aberration involving ETV6 may be a cause of myelodysplastic syndrome (MDS) with basophilia. Translocation t(5;12)(q31;p13) with ACSL6.
P41212	A chromosomal aberration involving ETV6 may be a cause of acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ACSL6.
P41212	A chromosomal aberration involving ETV6 is a cause of myelodysplastic syndrome (MDS). Translocation t(1;12)(p36.1;p13) with MDS2.
P41212	A chromosomal aberration involving ETV6 is a cause in many instances of chronic myeloproliferative disorder with eosinophilia (MPE) [MIM:131440]. Translocation t(5;12) with PDGFRB on chromosome 5 creating an ETV6-PDGFRB fusion protein.
P41212	Defects in ETV6 are a cause of acute myelogenous leukemia (AML) [MIM:601626]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development.
P41212	A chromosomal aberration involving ETV6 is a cause of acute lymphoblastic leukemia. Translocation t(9;12)(p13;p13) with PAX5.
P57679	Defects in EVC are a cause of Ellis-van Creveld syndrome (EVC) [MIM:225500]; also known as chondroectodermal dysplasia. EVC is an autosomal recessive disorder characterized by the clinical tetrad of chondrodystrophy, polydactyly, ectodermal dysplasia and cardiac anomalies. Patients manifest short-limb dwarfism, short ribs, postaxial polydactyly and dysplastic nails and teeth. Congenital heart defects, most commonly an atrioventricular septal defect, are observed in 60% of affected individuals.
P57679	Defects in EVC are a cause of acrofacial dysostosis Weyers type (WAD) [MIM:193530]; also known as Curry-Hall syndrome. Acrofacial dysostoses are a heterogeneous group of disorders combining limb defects with facial abnormalities. WAD is an autosomal dominant disorder characterized by dysplastic nails, postaxial polydactyly, acrofacial dysostosis, short limbs and short stature. The phenotype is milder than Ellis-van Creveld syndrome.
Q5HYI1	A chromosomal aberration involving EVI1 is a cause of chronic myelogenous leukemia (CML). Translocation t(3;21)(q26;q22) with RUNX1/AML1.
P20934	Expression of this gene is altered by viral integration and this altered expression may predispose cells to myeloid disease.
O60447	A chromosomal aberration involving EVI5 is found is a patient with stage 4S neuroblastoma. Translocation t(1;10)(p22;q21) that forms a EVI5-TRNG10 fusion protein. TRNG10 is a probable structural transcript which is normally not translated.
Q01844	Chromosomal aberrations involving EWSR1 are a cause of Ewing sarcoma [MIM:612219]. Translocation t(11;22)(q24;q12) with FLI1; translocation t(7;22)(p22;q12) with ETV1; translocation t(21;22)(q22;q12) with ERG; translocation t(9;22)(q22-31;q11-12) with NR4A3. Translocation t(2;21;22)(q23;q22;q12) that forms a EWSR1-FEV fusion protein with potential oncogenic activity.
Q01844	A chromosomal aberration involving EWSR1 is associated with desmoplastic small round cell tumor (DSRCT). Translocation t(11;22)(p13;q12) with WT1.
Q01844	A chromosomal aberration involving EWSR1 is associated with malignant melanoma of soft parts (MMSP). Translocation t(12;22)(q13;q12) with ATF-1. Malignant melanoma of soft parts, also known as soft tissue clear cell sarcoma, is a rare tumor developing in tendons and aponeuroses.
Q01844	A chromosomal aberration involving EWSR1 is associated with small round cell sarcoma. Translocation t(11;22)(p36.1;q12) with PATZ1.
Q01844	Chromosomal aberrations involving EWSR1 are associated with angiomatoid fibrous histiocytoma (AFH) [MIM:612160]. Translocation t(12;22)(q13;q12) with ATF1 generates a chimeric EWSR1/ATF1 protein. Translocation t(2;22)(q33;q12) with CREB1 generates a EWSR1/CREB1 fusion gene that is most common genetic abnormality in this tumor type.
Q16394	Defects in EXT1 are a cause of hereditary multiple exostoses type 1 (EXT1) [MIM:133700]. EXT is a genetically heterogeneous bone disorder caused by genes segregating on human chromosomes 8, 11, and 19 and designated EXT1, EXT2 and EXT3 respectively. EXT is a dominantly inherited skeletal disorder primarily affecting endochondral bone during growth. The disease is characterized by formation of numerous cartilage-capped, benign bone tumors (osteocartilaginous exostoses or osteochondromas) that are often accompanied by skeletal deformities and short stature. In a small percentage of cases exostoses have exhibited malignant transformation resulting in an osteosarcoma or chondrosarcoma. Osteochondromas development can also occur as a sporadic event.
Q16394	Defects in EXT1 are the cause of multiple exostoses observed in Langer-Giedon syndrome (LGS) [MIM:150230]; also known as trichorhinophalangeal syndrome type 2 (TRPS2). It is a contiguous gene syndrome due to deletions in chromosome 8q24.1 and resulting in the loss of functional copies of EXT1 and TRPS1.
Q16394	Defects in EXT1 may be a cause of chondrosarcoma [MIM:215300].
Q93063	Defects in EXT2 are a cause of hereditary multiple exostoses type 2 (EXT2) [MIM:133701]. EXT is a genetically heterogeneous bone disorder caused by genes segregating on human chromosomes 8, 11, and 19 and designated EXT1, EXT2 and EXT3 respectively. EXT is a dominantly inherited skeletal disorder primarily affecting endochondral bone during growth. The disease is characterized by formation of numerous cartilage-capped, benign bone tumors (osteocartilaginous exostoses or osteochondromas) that are often accompanied by skeletal deformities and short stature. In a small percentage of cases exostoses have exhibited malignant transformation resulting in an osteosarcoma or chondrosarcoma. Osteochondromas development can also occur as a sporadic event.
Q93063	Defects in EXT2 are the cause of multiple exostoses observed in Potocki-Shaffer syndrome [MIM:601224]. It is a contiguous gene syndrome due to proximal deletion of chromosome 11p11.2, including EXT2 and ALX4.
Q99502	Defects in EYA1 are the cause of branchiootorenal syndrome type 1 (BOR1) [MIM:113650]; also known as Melnick-Fraser syndrome. BOR is an autosomal dominant disorder manifested by various combinations of preauricular pits, branchial fistulae or cysts, lacrimal duct stenosis, hearing loss, structural defects of the outer, middle, or inner ear, and renal dysplasia. Associated defects include asthenic habitus, long narrow facies, constricted palate, deep overbite, and myopia. Hearing loss may be due to mondini type cochlear defect and stapes fixation. Penetrance of BOR syndrome is high, although expressivity can be extremely variable.
Q99502	Defects in EYA1 are the cause of otofaciocervical syndrome [MIM:166780]. The syndrome is characterized by trophic alterations of the facies and shoulder girdle in addition to the malformations seen in BOR.
Q99502	Defects in EYA1 are the cause of branchiootic syndrome type 1 (BOS1) [MIM:602588]; also known as BO syndrome type 1 or branchiootic dysplasia. Individuals with BOS1 are affected by the same branchial and otic anomalies as those seen in individuals with BOR1, but lack renal anomalies.
O95677	Defects in EYA4 are the cause of non-syndromic sensorineural deafness autosomal dominant type 10 (DFNA10) [MIM:601316]. DFNA10 is a form of sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information.
O95677	Defects in EYA4 are the cause of cardiomyopathy dilated type 1J (CMD1J) [MIM:605362]. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Q5T3C8	Defects in EYS are the cause of retinitis pigmentosa type 25 (RP25) [MIM:602772]. RP leads to degeneration of retinal photoreceptor cells. Patients suffer from night blindness, beginning at approximately 25 years of age, and deterioration of visual acuity (central vision), beginning at approximately 30 years of age. By age 55 to 60 years, many affected subjects have no perception of light in either eye.
Q9H6L5	Defects in FAM134B are a cause of hereditary sensory and autonomic neuropathy type 2 (HSAN2) [MIM:201300]; also known as hereditary sensory radicular neuropathy, or neurogenic acroosteolysis. The hereditary sensory and autonomic neuropathies are a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN2 is an autosomal recessive disorder characterized by impairment of pain, temperature and touch sensation, onset of symptoms in infancy or early childhood, occurrence of distal extremity pathologies (paronychia, whitlows, ulcers, and necrosis Charcot joints), frequent amputations, sensory loss that affects all modalities of sensation (lower and upper limbs and perhaps the trunk as well), absence or diminution of tendon reflexes (usually in all limbs), minimal autonomic dysfunction, absence of sensory nerve action potentials, and virtual absence of myelinated fibers with decreased numbers of unmyelinated fibers in sural nerves.
P00488	Defects in F13A1 are the cause of F13A deficiency [MIM:134570]. F13A deficiency is an autosomal recessive disorder characterized by a life-long bleeding tendency, impaired wound healing and spontaneous abortion in affected women. In addition to the common presentation such as subcutaneous and intramuscular haematomas, severe bleeding such as intracranial hemorrhages may occur.
P09467	Defects in FBP1 are the cause of fructose-1,6- bisphosphatase deficiency (FBPD) [MIM:229700]. FBPD is inherited as an autosomal recessive disorder mainly in the liver and causes life-threatening episodes of hypoglycemia and metabolic acidosis (lactacidemia) in newborn infants or young children.
Q5NTB3	Defects in F11 are the cause of factor XI deficiency in Japanese black cattle. It is an hereditary mild bleeding disorder with an autosomal recessive mode of inheritance.
P03951	Defects in F11 are the cause of F11 deficiency [MIM:612416]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a blood coagulation abnormality occurring in high frequency in Ashkenazi jews. F11- deficient patients are prone to excessive bleeding after haemostatic challenge.
P00748	Defects in F12 are the cause of factor XII deficiency (FA12D) [MIM:234000]; also known as Hageman factor deficiency. This trait is an asymptomatic anomaly of in vitro blood coagulation. Its diagnosis is based on finding a low plasma activity of the factor in coagulating assays. It is usually only accidentally discovered through pre-operative blood tests. F12 deficiency is divided into two categories, a cross-reacting material (CRM)-negative group (negative F12 antigen detection) and a CRM-positive group (positive F12 antigen detection).
P00748	Defects in F12 are the cause of hereditary angioedema type 3 (HAE3) [MIM:610618]; also known as estrogen-related HAE or hereditary angioneurotic edema with normal C1 inhibitor concentration and function. HAE is characterized by episodic local subcutaneous edema, and submucosal edema involving the upper respiratory and gastrointestinal tracts. HAE3 occurs exclusively in women and is precipitated or worsened by high estrogen levels (e.g., during pregnancy or treatment with oral contraceptives). It differs from HAE types 1 and 2 in that both concentration and function of C1 inhibitor are normal.
Q7L5A8	Defects in FA2H are the cause of leukodystrophy dysmyelinating with spastic paraparesis with or without dystonia (DLDSP) [MIM:612443]. The disorder consists of a progressive neurologic disease manifested by spasticity, disordered tonicity of muscle, and white matter degeneration.
Q8N1B3	Defects in FAM58A are the cause of toe syndactyly, telecanthus, and anogenital and renal malformations (STAR) [MIM:300707]; also known as STAR syndrome or syndactyly with renal and anogenital malformations.
P12259	Defects in F5 are the cause of factor V deficiency (FA5D) [MIM:227400]; also known as Owren parahemophilia. It is an hemorrhagic diastesis.
P12259	Defects in F5 are the cause of thrombophilia due to activated protein C resistance (THR-APCR) [MIM:188055]. THR-APCR is a hemostatic disorder due to defective degradation of factor Va by activated protein C. It is characterized by a poor anticoagulant response to activated protein C resulting in tendency to thrombosis.
P12259	Defects in F5 are a cause of susceptibility to Budd- Chiari syndrome [MIM:600880]. Budd-Chiari syndrome is a spectrum of disease states, including anatomic abnormalities and hypercoagulable disorders, resulting in hepatic venous outflow occlusion. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain, and abdominal ascites.
P12259	Defects in F5 may be a cause of susceptibility to ischemic stroke [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.
P08709	Defects in F7 are the cause of F7 deficiency [MIM:227500]; also known as factor VII deficiency. F7 deficiency is a rare hereditary hemorrhagic disease. The clinical picture can be very severe, with the early occurrence of intracerebral hemorrhages or hemarthroses, or, in contrast, moderate with cutaneous-mucosal hemorrhages (epistaxis, menorrhagia) or hemorrhages provoked by a surgical intervention. Numerous subjects are completely asymptomatic despite a very low F7 level.
Q6ZRV2	Defects in FAM83H are the cause of amelogenesis imperfecta type 3 (AI3) [MIM:130900]. AI3 is an autosomal dominant hypomineralized form of amelogenesis imperfecta, a defect of enamel formation. AI3 is characterized by enamel of normal thickness, but soft and with cheesy consistency. Enamel is lost from tooth soon after eruption.
P00451	Defects in F8 are the cause of hemophilia A (HEMA) [MIM:306700]. HEMA is a common recessive X-linked coagulation disorder. The frequency of hemophilia A is 1-2 in 10,000 male births in all ethnic groups. About 50% of patients have severe hemophilia A with F8C activity less than 1% of normal; they have frequent spontaneous bleeding into joints, muscles and internal organs. Moderately severe hemophilia A occurs in about 10% of patients; F8C activity is 2-5% of normal, and there is bleeding after minor trauma. Mild hemophilia A, which occurs in 30-40% of patients, is associated with F8C activity of 5-30% and bleeding occurs only after significant trauma or surgery. Of particular interest for the understanding of the function of F8C is the category of CRM (cross-reacting material) positive patients (approximately 5%) that have considerable amount of F8C in their plasma (at least 30% of normal), but the protein is non- functional; i.e., the F8C activity is much less than the plasma protein level. CRM-reduced is another category of patients in which the F8C antigen and activity are reduced to approximately the same level. Most mutations are CRM negative, and probably affect the folding and stability of the protein.
Q6ZTR7	Genetic variations in FAM92B may be associated with susceptibility to inflammatory bowel disease type 10 (IBD10) [MIM:611081]. IBD is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease (CD) and ulcerative colitis phenotypes. IBD10 individuals show the phenotype characteristic to CD. It may involve any part of the gastrointestinal tract, but most frequently the terminal ileum and colon. CD is commonly classified as autoimmune disease.
P19540	Defects in F9 are the cause of hemophilia B (HEMB).
P00740	Defects in F9 are the cause of recessive X-linked hemophilia B (HEMB) [MIM:306900]; also known as Christmas disease.
P00740	Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide, mutation in position 93 (Alabama) probably fails to bind to cell membranes, mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya OR Hilo) prevent cleavage of the activation peptide.
P16930	Defects in FAH are the cause of tyrosinemia type 1 (TYRO1) [MIM:276700]. TYRO1 is an inborn error of metabolism characterized by elevations of tyrosine in the blood and urine, and hepatorenal manifestations. Typical features include hepatic necrosis, renal tubular injury, episodic weakness, self- mutilation, and seizures. Renal tubular dysfunction is associated with phosphate loss and hypophosphataemic rickets. Progressive liver disease can lead to the development of hepatocellular carcinoma. Dietary treatment with restriction of tyrosine and phenylalanine alleviates the rickets, but liver transplantation has so far been the only definite treatment. TYRO1 is a rare condition, except in the Saguenay-lac-St-Jean region (province of Quebec, Canada) where the frequency is high as the result of a founder effect.
Q9BXW9	Defects in FANCD2 are a cause of Fanconi anemia (FA) [MIM:227650]. FA is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
O75844	Defects in ZMPSTE24 are the cause of mandibuloacral dysplasia with type B lipodystrophy (MADB) [MIM:608612]. Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, joint contractures, and types A or B patterns of lipodystrophy. Type B lipodystrophy observed in MADB, is characterized by generalized fat loss.
O75844	Defects in ZMPSTE24 are a cause of lethal tight skin contracture syndrome [MIM:275210]; also called restrictive dermopathy (RD). Lethal tight skin contracture syndrome is a rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance.
Q9UEL9	Defects in FANCA are a cause of Fanconi anemia (FA) [MIM:227650]. FA is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
Q8NB91	Defects in FANCB are the cause of Fanconi anemia complementation group B (FANCB) [MIM:300514]; also known as Fanconi pancytopenia type 2 (FA2). Fanconi anemia (FA) [MIM:227650] is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
Q8NB91	Defects in FANCB are the cause of X-linked VACTERL-H (XVACTERL-H) [MIM:314390]; also known as X-linked VACTERL association with hydrocephalus syndrome. VACTERL is an acronym for vertebral anomalies, anal atresia, cardiac malformations, tracheoesophageal fistula, renal anomalies (urethral atresia with hydronephrosis), and limb anomalies (hexadactyly, humeral hypoplasia, radial aplasia, and proximally placed thumb). Some cases of VACTERL-H are associated with increased chromosome breakage and rearrangement.
Q00597	Defects in FANCC are a cause of Fanconi anemia (FA) [MIM:227650]. FA is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
Q9HB96	Defects in FANCE are a cause of Fanconi anemia (FA) [MIM:227650]. FA is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
Q9NPI8	Defects in FANCF are a cause of Fanconi anemia (FA) [MIM:227650]. FA is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
O15287	Defects in FANCG are a cause of Fanconi anemia (FA) [MIM:227650]. FA is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
Q9NVI1	Defects in FANCI are a cause of Fanconi anemia complementation group I (FANCI) [MIM:609053]. Fanconi anemia (FA) [MIM:227650] is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
Q9BX63	Defects in BRIP1 are a cause of susceptibility to breast cancer (BC) [MIM:114480]. BC is an extremely common malignancy, affecting one in eight women during their lifetime. A positive family history has been identified as major contributor to risk of development of the disease, and this link is striking for early- onset breast cancer.
Q9BX63	Defects in BRIP1 are the cause of Fanconi anemia complementation group J (FANCJ) [MIM:609054]. Fanconi anemia (FA) [MIM:227650] is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.
Q9NW38	Defects in FANCL are a cause of Fanconi anemia (FA) [MIM:227650]. FA is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
Q9CR14	Defects in Fancl are a cause of the gcd (germ cell deficient) mutant phenotype, which leads to reduced numbers of precursor germ cells and adult sterility, probably due to a reduced precursor germ cells proliferation.
Q8IYD8	Defects in FANCM are a cause of Fanconi anemia (FA) [MIM:227650]. FA is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair.
Q9UC21	A chromosomal aberration involving FBLN1 is found in a complex type of synpolydactyly, also referred to as 3/3-prime/4 synpolydactyly associated with metacarpal and metatarsal synostoses [MIM:608180]. Reciprocal translocation t(12;22)(p11.2;q13.3) with C12orf2. Fibroblasts derived from a patient with synpolydactyly displayed alterations in the level of isoform D splice variant incorporated into the ECM and secreted into the conditioned culture medium. By contrast, the expression of isoform C was not perturbed in the patient's fibroblasts. Furthermore, no aberrant polypeptides were detected in extracts of cultured patient's fibroblasts. The translocation t(12;22) may result in haploinsufficiency of the isoform D splice variant, which could lead to the observed limb malformation.
Q9UC21	Elevated expression and altered processing of FBLN1 protein is associated with human breast cancer.
Q12805	Defects in EFEMP1 are a cause of Doyne honeycomb retinal dystrophy (DHRD) [MIM:126600]; also known as malattia leventinese (MLVT) (ML). DHRD is an autosomal dominant disease characterized by yellow-white deposits known as drusen that accumulate beneath the retinal pigment epithelium.
O95967	Defects in EFEMP2 are a cause of autosomal recessive cutis laxa type I (CL type I) [MIM:219100]. Hereditary cutis laxa refers to a heterogeneous group of connective tissue disorders characterized by cutaneous abnormalities and variable systemic manifestations. The most constant clinical feature is loose skin, sagging over the face and trunk. Hereditary cutis laxa is inherited in both autosomal dominant and autosomal recessive modes. CL type I shows the most severe phenotype and has the poorest prognosis. In addition to the skin, internal organs enriched in elastic fibers, such as the lung and arteries, are affected.
Q9UBX5	Defects in FBLN5 are a cause of autosomal dominant cutis laxa [MIM:123700]. Hereditary cutis laxa refers to a heterogeneous group of connective tissue disorders characterized by cutaneous abnormalities and variable systemic manifestations. The most constant clinical feature is loose skin, sagging over the face and trunk. Hereditary cutis laxa is inherited in both autosomal dominant and autosomal recessive modes. Autosomal dominant cutis laxa is a relatively benign inherited and acquired connective tissue disorder.
Q9UBX5	Defects in FBLN5 are a cause of autosomal recessive cutis laxa type I (CL type I) [MIM:219100]. CL type I shows the most severe phenotype and has the poorest prognosis. In addition to the skin, internal organs enriched in elastic fibers, such as the lung and arteries, are affected.
Q9UBX5	Defects in FBLN5 are the cause of age-related macular degeneration type 3 (ARMD3) [MIM:608895]. ARMD is a multifactorial disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
P35555	Defects in FBN1 are a cause of Marfan syndrome (MFS) [MIM:154700]. MFS is an autosomal dominant disorder that affects the skeletal, ocular, and cardiovascular systems. A wide variety of skeletal abnormalities occurs with MFS, including scoliosis, chest wall deformity, tall stature, abnormal joint mobility. Ectopia lentis occurs in up to about 80% of MFS patients and is almost always bilateral. The leading cause of premature death in MFS patients is progressive dilation of the aortic root and ascending aorta, causing aortic incompetence and dissection. The majority of the more than 600 mutations in FBN1 currently known are point mutations, the rest are frameshifts and splice site mutations. Marfan syndrome has been suggested in at least 2 historical figures, Abraham Lincoln and Paganini.
P35555	Defects in FBN1 are a cause of isolated ectopia lentis (EL) [MIM:129600]. The symptoms of this autosomal dominant fibrillinopathy overlap with those of Marfan syndrome, with the exclusion of the skeletal and cardiovascular manifestations.
P35555	Defects in FBN1 are the cause of Weill-Marchesani syndrome autosomal dominant (ADWMS) [MIM:608328]. A rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities including microspherophakia, ectopia lentis, severe myopia and glaucoma.
P35555	Defects in FBN1 are a cause of Shprintzen-Goldberg craniosynostosis syndrome (SGS) [MIM:182212]. SGS is a very rare syndrome characterized by a marfanoid habitus, craniosynostosis, characteristic dysmorphic facial features, skeletal and cardiovascular abnormalities, mental retardation, developmental delay and learning disabilities.
P35555	Defects in FBN1 are a cause of MASS syndrome [MIM:604308]. MASS syndrome is a heritable disorder of connective tissue characterized by involvement of the mitral valve, aorta, skeleton, and skin. MASS syndrome is closely resembling both the Marfan syndrome and the Barlow syndrome. However, no dislocation of the lenses or aneurysmal changes occur in the aorta, and the mitral valve prolapse is by no means invariable.
P35556	Defects in FBN2 are the cause of congenital contractural arachnodactyly (CCA) [MIM:121050]; also known as Beals syndrome or distal arthrogryposis type 9 (DA9). CCA is a rare, autosomal dominant connective tissue disorder characterized by contractures, arachnodactyly, scoliosis, and crumpled ears. Phenotypically similar to Marfan syndrome, CCA does not affect the aorta and the eyes.
Q60791	Identified as a product of a subpopulation of CD4+ lymphocytes resident in the hepatic egg granulomas in a murine model of Schistosoma mansoni. Circulating fibrosin levels increased after week 4 of infection, reached a peak at week 8, and normalized by week 12. It might be a useful marker of hepatic fibrogenesis in schistosomiasis. May also contribute to alcohol- induced hepatic fibrosis.
Q8TCJ0	A chromosomal aberration involving FBXO25 is a cause of X-linked mental retardation (XLMR). Translocation t(X;8)(p11.22;p23.3) with SHROOM4.
Q9Y3I1	Defects in FBXO7 may be the cause of parkinsonian- pyramidal syndrome (PKPS) [MIM:260300]. PKPS is a hypokinetic rigid disorder, the most common example of which is Parkinson disease. PKPS is a rare disorder that exhibits both Parkinsonian and pyramidal-associated signs. Symptoms, which may bevague in the beginning, start in young adulthood, progress relatively slowly, and may culminate in severe movement incapacity. Response to levadopa is usually dramatic and sustained for many years. Most, but not all, reported cases have been familial and associated with parental consanguinity, suggesting autosomal-recessive inheritance.
P57775	Defects in FBXW4 are a cause of split-hand/foot malformation type 3 (SHFM3) [MIM:600095]. SHFM3 is an autosomal dominant disorder characterized by hypoplasia/aplasia of the central digits with fusion of the remaining digits.
P31994	A chromosomal aberration involving FCGR2B is found in a follicular lymphoma. Translocation t(1;22)(q22;q11). The translocation leads to the hyperexpression of the receptor. This may play a role in the tumor progression.
Q96P29	Genetic variation in FCRL3 may be associated with susceptibility to rheumatoid arthritis [MIM:180300]. Rheumatoid arthritis is a complex, multifactorial disorder. It is one of the most common autoimmune diseases and it is characterized by inflammation of synovial tissue and joint destruction.
Q96P29	Genetic variation in FCRL3 is associated with susceptibility to Graves disease (GD) [MIM:275000]. GD is an autoimmune thyroid disease in which antibodies to the thyrotropin receptor result in constitutive activation of the receptor and increased levels of thyroid hormone.
Q96PJ5	A chromosomal aberration involving FCRL4 is found in non- Hodgkin lymphoma (NHG). Translocation t(1;1)(p36.3; q21.1-2).
Q96PJ5	A chromosomal aberration involving FCRL4 is found in multiple myeloma (MM). Translocation t(1;14)(q21;q32) that forms a FCRL4-IGHA1 fusion protein.
Q96RD9	A chromosomal aberration involving FCRL5 is found in Burkitt lymphoma (BL) cell lines with 1q21 abnormalities [MIM:113970]. Duplication dup(1)(q21q32).
Q9BQL6	Defects in FERMT1 are the cause of Kindler syndrome [MIM:173650]. Kindler syndrome is an autosomal recessive disorder characterized by neonatal blistering, sun sensitivity, atrophy, abnormal pigmentation and fragility of the skin.
Q99581	Genetic variation in FEV may be associated with susceptibility to sudden infant death syndrome (SIDS) [MIM:272120]. SIDS remains elusive in its causes and devastating in its consequences. Despite the impressive decline in the incidence of SIDS since the recommendation to avoid the prone sleep position, SIDS remains a leading cause of death in the first year of life.
Q99581	A chromosomal aberration