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

被引：574

作者：

Inoue, H

Tanizawa, Y

Wasson, J

Behn, P

Kalidas, K

Bernal-Mizrachi, E

Mueckler, M

Marshall, H

Donis-Keller, H

Crock, P

Rogers, D

Mikuni, M

Kumashiro, H

Higashi, K

Sobue, G

Oka, Y

Permutt, MA ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Internal Med, Div Endocrinol Diabet & Metab, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Dept Cell Biol, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Surg, Div Human Mol Genet, St Louis, MO 63110 USA

[4] Yamaguchi Univ, Sch Med, Dept Internal Med 3, Ube, Yamaguchi 755, Japan

[5] John Hunter Hosp, Newcastle, NSW, Australia

[6] Cleveland Clin Fdn, Div Pediat, Cleveland, OH 44195 USA

[7] Gunma Univ, Sch Med, Dept Neuropsychiat, Gunma, Japan

[8] Fukushima Med Coll, Dept Neuropsychiat, Fukushima, Japan

[9] Fujiwara Mem Hosp, Akita, Japan

[10] Nagoya Univ, Sch Med, Dept Neurol, Nagoya, Aichi 466, Japan

来源：

NATURE GENETICS | 1998年 / 20卷 / 02期

关键词：

D O I：

10.1038/2441

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 beta-cells and neurons.

引用

页码：143 / 148

页数：6

共 34 条

[31]

ROTTER JI, 1990, DIABETES MELLITUS TH, P378

[32] Predisposition of Wolfram syndrome heterozygotes to psychiatric illness [J].