title: Wolfram syndrome in French population: characterization of novel mutations and polymorphisms in the WFS1 gene.
abstract: Wolfram syndrome (WS), a rare autosomal recessive neurodegenerative disorder, results in most cases from mutations in the WFS1 gene. In this study, a total of 19 patients with Wolfram syndrome and 36 relatives from 17 families were screened for mutations in the WFS1 gene. WFS1 mutations were identified on both alleles in 16 of 19 patients and on 1 allele of 3 patients, showing that WFS1 is the major gene involved in WS in the french population. We identified 25 different mutations, twelve of which were novel. We found 6 frameshift mutations, 6 nonsense mutations, 6 missense mutations, 6 in-frame deletions, and one new homozygous mutation in the splice donor site of exon 7 (c.861+1G>A) resulting in a frameshift. Most patients were compound heterozygotes. No common founder mutation or mutational hot spot were found in the WFS1 gene. Although most mutations occurred in exon 8, in some cases molecular screening requires analysis of all exons, including the non-coding exon 1. We also identified 3 new polymorphisms. Furthermore, genotype-phenotype correlation suggests that the presence of inactivating mutations on both alleles may be associated with an early onset of diabetes mellitus.
authors.affiliation: Department of Medical Genetics, Hopital Archet 2, Nice, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Giuliano
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bannwarth
authors.forename: Sophie
authors.initials: S
authors.lastname: Monnot
authors.forename: Aline
authors.initials: A
authors.lastname: Cano
authors.forename: Brigitte
authors.initials: B
authors.lastname: Chabrol
authors.forename: Bernard
authors.initials: B
authors.lastname: Vialettes
authors.forename: Bruno
authors.initials: B
authors.lastname: Delobel
authors.forename: Veronique
authors.initials: V
authors.lastname: Paquis-Flucklinger
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D014929:Wolfram Syndrome / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein