A novel connexin46 (GJA3) mutation in autosomal dominantcongenital nuclear pulverulent cataract

[摘要] Purpose: To report the identification of a novel mutation ofconnexin46 in a large Chinese family with autosomal dominant congenitalnuclear pulverulent cataract.Methods: Genetic linkage analysis was performed on the known geneticloci for autosomal dominant congenital nuclear pulverulent cataract witha panel of polymorphic markers and mutations were screened by directsequencing.Results: Significant two point lod score was generated at markerD13S175 (Zmax=3.61, θ=0), further linkage and haplotypestudies confined the disease locus to 13q11-13. Mutation screening ofconnexin46 in this family revealed an A->C transition at position 563(N188T) of the cDNA sequence, creating a novel AleI restriction sitethat co-segregated with affected members of the pedigree, but was notpresent in unaffected relatives or 100 normal individuals.Conclusions: Our finding expands the spectrum of connexin46mutations causing autosomal dominant congenital nuclear pulverulentcataract, and confirms the role of connexin46 in the pathogenesis ofautosomal dominant congenital nuclear pulverulent cataract.

[学科分类] 生物化学/生物物理