Identification of a novel mutation of the gene for gap junction protein α3 (GJA3) in a Chinese family with congenital cataract
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Cataract, defined as any opacity of the crystallin lens, can be divided into early onset (congenital or infantile) and age-related. It is the leading cause of visual disability in children, and mutations in many genes have currently been linked with this disorder. In the present study, we identified a genetic defect in a Chinese family with congenital cataract. Genomic DNA was extracted from the venous blood of the family and 100 normal controls. To screen for the disease-causing mutation, we sequenced eight candidate genes, and to predict the functional consequences of the mutation, a structural model of the protein was developed using the Protein Data Bank and PyMOL 1.1r1. We found a novel variant (c.163 A > G transition) in the gene for gap junction protein α3, or the connexin46 gene. This mutation resulted in the substitution of a highly conserved asparagine at codon 55 by aspartic acid (p.N55D). There were no nucleotide polymorphisms in the other candidate genes sequenced.
KeywordsCongenital cataract Gap junction protein α3 Mutation Structural analysis
The authors are grateful to all patients and their family as well as to the normal volunteers for their participation in this research. This study was supported by the National Natural Science Foundation of China (81070730, 81271000), the Key Program of Natural Science Foundation of Heilongjiang Province (ZD201015), and the Foundation of Health Department of Heilongjiang Province (2011-054).
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