Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein

被引:369
作者
Strom, TM
Hörtnagel, K
Hofmann, S
Gekeler, F
Scharfe, C
Rabl, W
Gerbitz, KD
Meitinger, T
机构
[1] Univ Munich, Klinikum Innenstadt, Abt Med Genet, D-80336 Munich, Germany
[2] Akad Lehrkrankenhaus Munchen Schwabing, Inst Klin Chem, D-80804 Munich, Germany
[3] Akad Lehrkrankenhaus Munchen Schwabing, Kinderklin, D-80804 Munich, Germany
[4] Univ Munich, Klinikum Grosshadern, Neurol Klin, D-81377 Munich, Germany
关键词
D O I
10.1093/hmg/7.13.2021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Wolf ram 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 Wolf ram 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 Wolf ram syndrome patients.
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页码:2021 / 2028
页数:8
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