Purpose: To identify the genetic defects in a three-generation Chinese family with congenital nuclear cataract.
Methods: Four patients and three healthy members from the family underwent complete physical and ophthalmic examinations. Genomic DNA was extracted from peripheral blood leukocytes of the family members as well as from 100 healthy normal controls. Polymerase chain reaction (PCR) amplification and direct sequencing of all coding exons of candidate genes were performed. The functional consequences of the mutation were analyzed with biology softwares.
Results: A novel mutation (c.130G>A) was identified in the connexin 46 gene (GJA3), which resulted in the substitution of valine by methionine at the highly conserved codon 44 of connexin 46. This mutation co-segregated among the affected members of the family and was not observed in either unaffected members or the 100 normal controls.
Conclusions: This is a novel missense mutation identified in the first extracellular loop of connexin 46; this expands the mutation spectrum of GJA3 in association with congenital cataract.