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.