Novel mutations in GJA3 associated with autosomal dominant congenital cataract in the Indian population.

PURPOSE: Connexin 46 (Cx46) is crucial in the maintenance of lens homeostasis and it is known to be expressed mainly in the terminally differentiated lens fiber cells. The present study aimed to identify the spectrum of mutations in Connexin 46 in the Indian population.

METHODS

PCR based Single Stranded Conformational Polymorphism (SSCP) analysis was used to screen sixty probands with nonsyndromic congenital cataract for mutations in the Cx46 gene (GJA3), followed by direct sequencing of samples that showed an electrophoretic shift. Mutation predicted to affect the coding sequence were subsequently analyzed in the entire pedigree.

RESULTS

Two novel missense mutations were identified in Cx46. The mutation in Family 1 was characterized as R76G with a total cataract phenotype. A V28M missense mutation was identified in family 2, the cataract phenotype varied in its severity and the age of onset. The mutation was also identified in 2 unaffected individuals of the family and the intrafamilial variation of the disease suggests the possibility of a modifier gene(s) or the effects of environmental factors being involved. The mutation was identified in all the affected members in the family and found to be absent in 400 ethnically matched control chromosomes analyzed.

CONCLUSIONS

We conclude that connexin 46 mutations might account for as much as 3.3% of the hereditary congenital cataract in the Indian population.