Mutational Analysis of the Wolfram Syndrome Gene (WFS1) in Greek and Dominican Patients

Wolfram syndrome is an autosomal recessive neurodegenerative disorder mapped to 4pl6 associated with juvenile-onset insulin-dependent diabetes mellitus and bilateral progressive optic nerve atrophy. The gene responsible for Wolfram syndrome, WFS1, is a member of a novel gene family whose function is currently undefined. In this study, mutational analysis of WFS1 was performed in three patients from two unrelated families with Wolfram syndrome as well as 35 Greek and 35 Dominican healthy controls. A novel mutation (1683-1697del15nt) was identified in a Greek patient with Wolfram syndrome, and a 1387delCTCT mutation that was previously identified in Italian patients was identified in two affected Dominican siblings. One novel coding variant (D771G) was also identified that is likely not pathogenic. Additionally, several novel polymorphisms of WFS1 were identified in control, unaffected individuals of Greek and Dominican descent. This study represents the first mutational analysis of WFS1 in Greek and Dominican patients with Wolfram syndrome and provides molecular reagents for analysis of this gene in non-syndromic diabetes mellitus, depression, and hearing loss.