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 neurodeg enerative disorder defined by young-onset non-immune insulin-dependent diabetes mellitus and progressive optic atrophy. Linkage to markers o n chromosome 4p was confirmed in five families. On the basis of meioti c recombinants and disease-associated haplotypes, the WFS gene was loc alized to a BAC/P1 contig of less than 250 kb. Mutations in a novel ge ne (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were ass ociated with the disease phenotype. WFS1 appears to function in surviv al of islet beta-cells and neurons.