Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wolfram syndrome is the association of diabetes mellitus and optic atrophy, also called DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). Incomplete characterisation has caused diagnostic confusion; we therefore undertook a nation-wide cross-sectional case finding study. We identified 45 patients with Wolfram syndrome, median age 29 years. All patients fulfilled the ascertainment criteria (juvenile onset diabetes mellitus and optic atrophy). Optic atrophy presented in 38 patients with reduced visual acuity and colour vision defect (median age 11 years), progressing to visual acuity of 6/60 or less in 35 patients (median time 8 years, range 1-25 years). Visual field examinations recorded before acuity deteriorated showed central scotomas with peripheral constriction. Blind patients had absent pupillary reflexes. Horizontal nystagmus was seen in patients with other signs of cerebellar degeneration. There was no pigmentary retinal dystrophy; only 3 patients had background diabetic retinopathy, despite a median duration of diabetes of 24 years. Electroretinography was normal in 3 patients and showed reduced amplitude in 3 patients; visual evoked responses were abnormal (10/10 patients: reduced amplitude to both flash and pattern stimulation). Magnetic resonance imaging showed generalised brain atrophy with reduced signal from the optic nerves and chiasm. A postmortem brain specimen from one patient revealed atrophy of the optic nerves, chiasm, cerebellum and brainstem. We found no evidence of mitochondrial genome defects or rearrangements. This primary neurogenerative disorder presents with diabetes mellitus and progressive optic atrophy, probably due to pathology in the optic nerve.
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PMID:Optic atrophy in Wolfram (DIDMOAD) syndrome. 953 52

Wolfram syndrome is an autosomal recessive disorder characterized by juvenile diabetes mellitus, diabetes insipidus, optic atrophy and a number of neurological symptoms including deafness, ataxia and peripheral neuropathy. Mitochondrial DNA deletions have been described in a few patients and a locus has been mapped to 4p16 by linkage analysis. Susceptibility to psychiatric illness is reported to be high in affected individuals and increased in heterozygous carriers in Wolfram syndrome families. We screened four candidate genes in a refined critical linkage interval covered by an unfinished genomic sequence of 600 kb. One of these genes, subsequently named wolframin, codes for a predicted transmembrane protein which was expressed in various tissues, including brain and pancreas, and carried loss-of-function mutations in both alleles in Wolfram syndrome patients.
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PMID:Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. 981 17

Recently, a novel gene for a putative transmembrane protein (WFS1/wolframin) was found to be mutated in patients with Wolfram syndrome or DI-DM-OA-D (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) syndrome. It is suggested that the WFS1 protein is important in the survival of islet beta-cells. We studied the WFS1 gene in a Japanese population to assess its possible role in common type 1 diabetes. Mutation screening revealed four missense mutations; R456H, G576S, H611R, and I720V. By genetic association studies of 185 type 1 diabetes patients and 380 control subjects, we found that R456H was significantly increased in the type 1 diabetes group compared to the control group (P = 0.0005); H611R and I720V were also significantly increased with weaker significance. Furthermore, in patients with the R456H mutation, type 1 diabetes-resistant HLA-DRB1 alleles (DRB1*0406, 1501, and 1502) were significantly increased compared to mutation-negative patients while susceptible DRB1*0901 was significantly decreased. Frequencies of autoimmunity characteristics (ICA or GAD-Ab positiveness and combination of autoimmune thyroid disease) were decreased in the R456H-positive patients compared to the R456H-negative patients. These data suggest that the WFS1 gene may have a role in the development of common type 1 diabetes as a nonautoimmune genetic basis.
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PMID:Missense variations of the gene responsible for Wolfram syndrome (WFS1/wolframin) in Japanese: possible contribution of the Arg456His mutation to type 1 diabetes as a nonautoimmune genetic basis. 1067 52

Identifying genetic loci at which mutations predispose individuals to common psychiatric illnesses will have major impact on the diagnosis and treatment of mental illness. The available evidence indicates that mutations at the Wolfram syndrome locus contribute substantially to the prevalence of psychiatric illness in the general population. Patients with mutations at this locus on both parental chromosomes, called Wolfram syndrome homozygotes, have a distinctive and rare autosomal recessive syndrome characterized by juvenile onset diabetes mellitus and bilateral progressive optic atrophy. Diverse and serious psychiatric manifestations frequently have been observed in Wolfram syndrome patients; however, the population burden of mental illness attributable to mutations at this locus is almost entirely from individuals who carry a single mutation, called Wolfram syndrome heterozygotes, who have no distinguishing physical characteristics but constitute approximately 1% of the population. Molecular genotyping of blood relatives of Wolfram syndrome patients has shown that Wolfram syndrome heterozygotes are 26-fold more likely than noncarriers to have a psychiatric hospitalization. Severe depression was the predominant finding in the test group studied. The prediction that approximately 25% of all patients hospitalized for depression are Wolfram syndrome heterozygotes now can be tested by mutation screening of hospitalized patients from the general population. Many other behavioral and cognitive difficulties also have been observed in Wolfram syndrome families. For each specific psychiatric abnormality, a "test group" of blood relatives within Wolfram syndrome families with that abnormality can be formed. By comparing the number of Wolfram syndrome heterozygotes found in each test group by molecular genotyping with the number expected under the null hypothesis, the index-test method can determine which clinical phenotypes result from mutations at the Wolfram syndrome locus. This method can be utilized to identify other loci at which mutations predispose individuals to psychiatric illnesses.
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PMID:Psychiatric disorders and mutations at the Wolfram syndrome locus. 1081 37

We present here two DIDMOAD syndrome cases (Diabetes Mellitus, Diabetes Insipidus, Optic Atrophy, Deafness) in a Turkish family. In the examination of the propositus who had consanguineous parents, diabetes mellitus, diabetes insipidus, optic atrophy, and deafness were observed in addition to myopia, juvenile glaucoma, posterior polar cataract, and dilatation of the urinary tract. Diabetes mellitus, diabetes inspidus, optic atrophy, deafness, myopia, and ventricular septal defect were observed in his elder brother. Juvenile onset diabetes mellitus, congenital glaucoma, deafness, and heart disease were the other remarkable findings observed in relatives to this family. Juvenile glaucoma, posterior polar cataract observed in our propositus, and myopia in both our DIDMOAD syndrome cases are the first ophthalmic manifestations described in the DIDMOAD syndrome.
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PMID:A DIDMOAD syndrome family with juvenile glaucoma and myopia findings. 1099 58

Dominantly inherited progressive hearing loss DFNA38 is caused by heterozygosity for a novel mutation in WFS1, the gene for recessively inherited Wolfram syndrome. Wolfram syndrome is defined by juvenile diabetes mellitus and optic atrophy and may include progressive hearing loss and other neurological symptoms. Heterozygotes for other Wolfram syndrome mutations generally have normal hearing. Dominant deafness defined by DFNA38 is more severe than deafness of Wolfram syndrome patients and lacks any syndromic features. In a six-generation kindred from Newfoundland, Canada, WFS1 Ala716Thr (2146 G-->A) was shared by all deaf members of the family and was specific to deaf individuals. The causal relationship between this missense mutation and deafness was supported by two observations based on haplotype and mutation analysis of the kindred. First, a relative homozygous for the mutation was diagnosed at age 3 years with insulin-dependent diabetes mellitus, the central feature of Wolfram syndrome. Second, two relatives with normal hearing had an identical haplotype to that defining DFNA38, with the exception of the base pair at position 2146. Other rare variants of WFS1 co-inherited with deafness in the family could be excluded as disease-causing mutations on the basis of this hearing-associated haplotype. The possibility that 'mild' mutations in WFS1 might be a cause of non-syndromic deafness in the general population should be explored.
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PMID:Non-syndromic progressive hearing loss DFNA38 is caused by heterozygous missense mutation in the Wolfram syndrome gene WFS1. 1170 38

Wolfram syndrome patients are mainly characterised by juvenile onset diabetes mellitus and optic atrophy. A synonym is the acronym DIDMOAD: diabetes insipidus, diabetes mellitus, optic atrophy, deafness. Diabetes insipidus and sensorineural high-frequency hearing impairment are important additional features. This rare autosomal recessively inherited neurodegenerative syndrome is caused by mainly inactivating mutations in the WFS1 gene. It is located at chromosome 4p16 and encodes wolframin, a transmembrane protein. No function has yet been ascribed to this protein.
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PMID:[From gene to disease; mutations in the WFS1-gene as the cause of juvenile type I diabetes mellitus with optic atrophy (Wolfram syndrome)]. 1205 30

The Wolfram syndrome is a rare dysmorphogenetic disease of autosomic recessive hereditary nature. The pathogenesis of the disease is still not well known. It is characterised by the presence of diabetes insipidus, diabetes mellitus, optic atrophy and deafness. Other anomalies, such as renal outflow tracts and multiple neurological disorders may develop later. In our case report the diabetes mellitus appeared at the age of 4; the hearing loss and renal disturbances at the age of 11; the optic atrophy at the age of 16. No signs of ataxia, diabetes insipidus and neurologic anomalies were found. The diagnosis of Wolfram syndrome is not always easy in the first stages of the disease. The suspect may come from the presence of a juvenile diabetes mellitus asssociated with optic atrophy. For the diagnosis a valid clue can be given from the results of some clinical tests such as the positivity of the visual evoked potentials and the retinogram reliefs and the exclusion of the autoimmune origin of the diabetes mellitus. Other signs such as the progressive sensorineural hearing loss, the presence of nystagmus and of urodynamic disturbances and renal complications makes the diagnosis of this syndrome easier.
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PMID:Wolfram syndrome. 1472 94

Wolfram syndrome (WFS) is a rare diffuse neurodegenerative disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, deafness, and a wide variety of central nervous system abnormalities. Insulin-dependent diabetes mellitus with optic nerve atrophy is sufficient criteria for the diagnosis. WFS is a devastating disease for the patients and their families. This study emphasizes the need for careful evaluation of cases having insulin-dependent diabetes mellitus and optic atrophy.
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PMID:Wolfram syndrome: case report and review of the literature. 1791 6

Wolfram syndrome (WFS) is a rare diffuse neurodegenerative disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, deafness, and a wide variety of central nervous system abnormalities. Insulin-dependent diabetes mellitus with optic nerve atrophy is a sufficient criterion for the diagnosis. WFS is a devastating disease for the patients and their families. This study emphasizes the need for careful evaluation of cases having insulin-dependent diabetes mellitus and optic atrophy.
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PMID:Wolfram syndrome: case report and review of the literature. 1798 88


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