A novel p.F206I mutation in Cx46 associated with autosomal dominant congenital cataract

PURPOSE: To identify the genetic defect in a Chinese family with bilateral congenital cataract. METHODS: A three-generation family was recruited in this study. Detailed family history and clinical data were recorded. Ten candidate genes were screened for causative mutations. Direct sequencing was performed to analyze the cosegregation of the genotype with the disease phenotype. RESULTS: Affected individuals presented embryonal nuclear opacities in the lens. Sequencing of the candidate genes showed a heterozygous c. 616T>A variation in the connexin 46 (Cx46) gene, which resulted in the replacement of a highly conserved phenylalanine by isoleucine at codon 206 (p. F206I). This mutation co-segregated with all affected individuals and was not observed in unaffected family members or ethnically matched controls. CONCLUSIONS: We report a novel mutation (p.F206I) in the fourth transmembrane domain of connexin 46. These findings thus expand the mutation spectrum of Cx46 in association with congenital cataract.