Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans |
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| Authors: | Vanita Berry Cheryl Gregory-Evans Warren Emmett Naushin Waseem Jacob Raby DeQuincy Prescott Anthony T Moore Shomi S Bhattacharya |
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| Affiliation: | 1.Department of Genetics, Institute of Ophthalmology, University College London, London, UK;2.Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada;3.Department of Cancer Biology, Faculty of Medical Sciences, Cancer Institute, University College London, London, UK;4.Wolfson Institute for Biomedical Research, University College London, London, UK;5.Moorfields Eye Hospital, London, UK |
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| 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. |
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| Keywords: | nuclear cataract linkage WFS1 gene heterogeneity |
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