A novel mutation in the connexin 46 (GJA3) gene associated with congenital cataract in a Chinese pedigree

PURPOSE: To identify the potential pathogenic mutation in a three-generation Chinese family with congenital nuclear pulverulent cataracts. METHODS: A three-generation pedigree was recruited for our study. Three patients and four healthy members of the family underwent a comprehensive clinical examination. Genomic DNA extracted from peripheral blood was amplified using the polymerase chain reaction (PCR) method and the exons of all candidate genes were sequenced. RESULTS: When sequencing the encoding regions of the candidate genes, a novel mutation (c.559C>T) was identified in the gap junction protein alpha 3 (GJA3) gene, which resulted in the substitution of highly conserved proline by serine at codon 187 (P187S). There was no noticeable nucleotide polymorphism in other candidate genes. The mutation co-segregated with all patients, but was absent in the healthy members and 100 normal individuals. CONCLUSIONS: The present study identified a novel mutation (c.559C>T) in the GJA3 gene associated with autosomal dominant pulverulent cataracts in a Chinese family. As the first report to relate p.P187S mutation in GJA3, it expands the mutation spectrum of GJA3 in association with congenital cataracts.