A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).
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.
Inoue
H
H
Third Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Tanizawa
Y
Y
Wasson
J
J
Behn
P
P
Kalidas
K
K
Bernal-Mizrachi
E
E
Mueckler
M
M
Marshall
H
H
Donis-Keller
H
H
Crock
P
P
Rogers
D
D
Mikuni
M
M
Kumashiro
H
H
Higashi
K
K
Sobue
G
G
Oka
Y
Y
Permutt
M A
MA
D000328:Adult; D001483:Base Sequence; D002648:Child; D002894:Chromosomes, Human, Pair 4; D003001:Cloning, Molecular; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D014929:Wolfram Syndrome / Q000235:genetics*
D008565:Membrane Proteins; C114987:wolframin protein