Mutation analysis of connexin ۵۰ gene among Iranian families with autosomal dominant cataracts

Objective(s): Childhood cataract is a genetically heterogeneous eye disorder that results in visual impairment. The aim of this study was to identify the genetic mutations of connexin ۵۰ gene among Iranian families suffered from autosomal dominant congenital cataracts (ADCC). Materials and Methods: Families, having at least two members with bilateral familial congenital cataract, were selected for the study. Probands were evaluated by detailed ophthalmologist’s examination, and the pedigree analysis was performed. PCR amplifications were performed corresponding to coding region and intron-exon boundaries of GJA۸, a candidate gene responsible for ADCC. PCR products were subjected to bidirectional sequencing, and the co-segregation of identified mutations was examined and finally, the impact of identified mutations on biological functions of GJA۸ was predicted by in silico examination. Results: Three different genetic alterations, including c.۱۳۰G>A (p.V۴۴M), c.۳۰۱G>T (p.R۱۰۱L) and c.۱۳۴G>T (p.W۴۵L) in GJA۸ gene were detected among three probands. Two identified mutations, W۴۵L and V۴۴M have been already reported, while the R۱۰۱L is a novel mutation and its co-segregation was examined. This mutation was exclusively detected in the ADCC and could not be found among the healthy control group. The result of bioinformatic studies of R۱۰۱L mutation predicted that this amino acid substitution within GJA۸ could be a disease-afflicting mutation due to its potential effect on the protein structure and biological function. Conclusion: Our results suggest that mutations of lens connexin genes such as GJA۸ gene could be one of the major mechanisms of cataract development, at least in a significant proportion of Iranian patients with ADCC.

کلیدواژه ها:

Cataract ، Congenital ، Connexine ۵۰ gene ، GJA۸ ، Mutation