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Article
Nature Genetics  20, 143 - 148 (1998)
doi:10.1038/2441

A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome)

Hiroshi Inoue1, Yukio Tanizawa1, Jon Wasson2, Philip Behn2, Kamini Kalidas2, Ernesto Bernal-Mizrachi2, Mike Mueckler3, Helen Marshall4, Helen Donis-Keller4, Patricia Crock5, Douglas Rogers6, Masahiko Mikuni7, Hisashi Kumashiro8, Koichiro Higashi9, Gen Sobue10, Yoshitomo Oka1 & M. Alan Permutt2

1  Third Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.

2  Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism,Washington University School of Medicine, St. Louis, Missouri, USA.

3  Department of Cell Biology,Washington University School of Medicine, St. Louis, Missouri, USA.

4  Department of Surgery, Division of Human Molecular Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.

5  Paediatric Endocrinology and Diabetes, John Hunter Children's Hospital, Newcastle, Australia.

6  Division of Pediatrics, Cleveland Clinic Foundation , Cleveland, Ohio, USA.

7  Department of Neuropsychiatry, Gunma University School of Medicine, Gunma, Japan.

8  Department of Neuropsychiatry, Fukushima Medical College , Fukushima, Japan.

9  Fujiwara Memorial Hospital, Akita, Japan.

10  Department of Neurology, Nagoya University School of Medicine, Nagoya, Japan.

Correspondence should be addressed to M. Alan Permutt apermutt@imgate.wustl.edu
Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative disorder defined by young-onset non-immune insulin-dependent diabetes mellitus and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed in five families. On the basis of meiotic recombinants and disease-associated haplotypes, the WFS gene was localized to a BAC/P1 contig of less than 250 kb. Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were associated with the disease phenotype. WFS1 appears to function in survival of islet -cells and neurons.

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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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