title: Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene.
abstract: Autosomal dominant optic atrophy (ADOA) is genetically heterogeneous, with OPA1 on 3q28 being the most prevalently mutated gene. Additional loci are OPA3, OPA4, and OPA5, located at 19q13.2, 18q12.2, and 22q12.1-q13.1, respectively. Mutations in the WFS1 gene, at 4p16.3, are associated with either optic atrophy (OA) as part of the autosomal recessive Wolfram syndrome or with autosomal dominant progressive low frequency sensorineural hearing loss (LFSNHL) without any ophthalmological abnormalities. Linkage and sequence mutation analyses of the ADOA candidate genes OPA1, OPA3, OPA4, and OPA5, including the genes WFS1, GJB2, and GJB6 associated with recessive inherited OA or dominant LFSNHL, were performed. We identified one novel WFS1 missense mutation E864K, c.2590G-->A in exon 8 that co-segregates with ADOA combined with hearing impairment and impaired glucose regulation. This is the first example of autosomal dominant optic atrophy and hearing loss associated with a WFS1 mutation, supporting the notion that mutations in WFS1 as well as in OPA1 may lead to ADOA combined with impaired hearing.
authors.affiliation: Department of Medical Biochemistry and Genetics, Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark. he@imbg.ku.dk
authors.forename: H
authors.initials: H
authors.lastname: Eiberg
authors.forename: L
authors.initials: L
authors.lastname: Hansen
authors.forename: B
authors.initials: B
authors.lastname: Kjer
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
authors.forename: M
authors.initials: M
authors.lastname: Bille
authors.forename: T
authors.initials: T
authors.lastname: Rosenberg
authors.forename: L
authors.initials: L
authors.lastname: Tranebjaerg
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D002874:Chromosome Mapping; D000072259:Connexin 26; D017630:Connexins; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D006319:Hearing Loss, Sensorineural / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D029241:Optic Atrophy, Autosomal Dominant / Q000150:complications / Q000175:diagnosis / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D017630:Connexins; C000607042:GJB2 protein, human; D008565:Membrane Proteins; C114987:wolframin protein; D000072259:Connexin 26