Purpose: To report the identification of a novel mutation of connexin46 in a large Chinese family with autosomal dominant congenital nuclear pulverulent cataract.
Methods: Genetic linkage analysis was performed on the known genetic loci for autosomal dominant congenital nuclear pulverulent cataract with a panel of polymorphic markers and mutations were screened by direct sequencing.
Results: Significant two point lod score was generated at marker D13S175 (Zmax=3.61, theta=0), further linkage and haplotype studies confined the disease locus to 13q11-13. Mutation screening of connexin46 in this family revealed an A->C transition at position 563 (N188T) of the cDNA sequence, creating a novel AleI restriction site that co-segregated with affected members of the pedigree, but was not present in unaffected relatives or 100 normal individuals.
Conclusions: Our finding expands the spectrum of connexin46 mutations causing autosomal dominant congenital nuclear pulverulent cataract, and confirms the role of connexin46 in the pathogenesis of autosomal dominant congenital nuclear pulverulent cataract.