title: Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans.
abstract: Congenital cataracts are an important cause of bilateral visual impairment in infants. Through genome-wide linkage analysis in a four-generation family of Irish descent, the disease-associated gene causing autosomal-dominant congenital nuclear cataract was mapped to chromosome 4p16.1. The maximum logarithm of odds (LOD) score was 2.62 at a recombination fraction θ=0, obtained for marker D4S432 physically close to the Wolfram gene (WFS1). By sequencing the coding regions and intron-exon boundaries of WFS1, we identified a DNA substitution (c.1385A-to-G) in exon 8, causing a missense mutation at codon 462 (E462G) of the Wolframin protein. This is the first report of a mutation in this gene causing an isolated nuclear congenital cataract. These findings suggest that the membrane trafficking protein Wolframin may be important for supporting the developing lens.
authors.affiliation: Department of Genetics, Institute of Ophthalmology, University College London, London, UK.
authors.forename: Vanita
authors.initials: V
authors.lastname: Berry
authors.forename: Cheryl
authors.initials: C
authors.lastname: Gregory-Evans
authors.forename: Warren
authors.initials: W
authors.lastname: Emmett
authors.forename: Naushin
authors.initials: N
authors.lastname: Waseem
authors.forename: Jacob
authors.initials: J
authors.lastname: Raby
authors.forename: DeQuincy
authors.initials: D
authors.lastname: Prescott
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
mesh_terms: D001483:Base Sequence; D002386:Cataract / Q000151:congenital* / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C114987:wolframin protein