Novel mutations in GJA3 associated with autosomal dominantcongenital cataract in the Indian population

[摘要] Purpose: Connexin 46 (Cx46) is crucial in the maintenance of lenshomeostasis and it is known to be expressed mainly in the terminallydifferentiated lens fiber cells. The present study aimed to identify thespectrum 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 nonsyndromiccongenital cataract for mutations in the Cx46 gene (GJA3), followedby direct sequencing of samples that showed an electrophoretic shift.Mutation predicted to affect the coding sequence were subsequentlyanalyzed in the entire pedigree.Results: Two novel missense mutations were identified in Cx46. Themutation in Family 1 was characterized as R76G with a total cataractphenotype. A V28M missense mutation was identified in family 2, thecataract phenotype varied in its severity and the age of onset. Themutation was also identified in 2 unaffected individuals of the familyand the intrafamilial variation of the disease suggests the possibilityof a modifier gene(s) or the effects of environmental factors beinginvolved. The mutation was identified in all the affected members in thefamily and found to be absent in 400 ethnically matched controlchromosomes analyzed.Conclusions: We conclude that connexin 46 mutations might accountfor as much as 3.3% of the hereditary congenital cataract in the Indianpopulation.

[学科分类] 生物化学/生物物理