A novel insertional mutation in the connexin 46 (gap junction alpha 3) gene associated with autosomal dominant congenital cataract in a Chinese family

PURPOSE To identify the genetic defect associated with autosomal dominant congenital cataract (ADCC) in a Chinese family, in which 11 individuals across four generations are affected with coralliform cataract. METHODS Exome sequencing was performed in two of the ADCC-affected family members to scan for potential genetic defects. Sanger sequencing was used to verify these defects in the whole family. RESULTS By combining whole exome sequencing and Sanger sequencing, the genetic defect was revealed to be a insertion of a cytosine after coding nucleotide 1,361 (1361insC) in the gap junction alpha 3 (GJA3) gene, causing a frameshift at codon 397 (p.Ala397Glyfs×71). This frameshift mutation cosegregates with the ADCC-affected pedigree members, but is absent in unaffected relatives and 100 normal individuals. CONCLUSIONS A 1361 insC mutation in the C-terminus of GJA3 is found to be associated with autosomal dominant congenital coralliform cataract. This finding is similar to that of a previous publication, thus providing further evidence that the GJA3 C-terminal domain is also its mutation area, and further expanding the mutation spectrum of GJA3 in association with congenital cataract.