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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 ?=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.

SUBMITTER: Berry V

PROVIDER: S-EPMC3831071 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans.

Berry Vanita V Gregory-Evans Cheryl C Emmett Warren W Waseem Naushin N Raby Jacob J Prescott DeQuincy D Moore Anthony T AT Bhattacharya Shomi S SS

European journal of human genetics : EJHG 20130327 12

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 boundarie ...[more]

PMID: 23531866

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