Novel Mutations in GJA8 Associated with Autosomal Dominant Congenital Cataract and Microcornea

Purpose: The purpose of this study was to estimate the importance of mutations in the connexin50 gene (GJA8) as a cause of congenital or developmental cataracts in the Indian population and to identify novel mutations in GJA8 that cause cataract in this population.

Methods: The coding region of GJA8 was analyzed for mutation by single strand conformational polymorphism in 60 probands affected with congenital or developmental cataract of which 11 probands' corneal diameter measured less than 11.00 mm. Direct sequencing was performed for samples that displayed an abnormal electrophoresis pattern. The segregation of the change with the diseased phenotype was analyzed in the entire pedigree by restriction fragment length polymorphism (RFLP) analysis.

Results: Molecular analysis of GJA8 revealed two novel missense mutations V44E and R198Q, in the population screened. The mutations cosegregated with the diseased phenotype in an autosomal dominant manner and were absent in 400 normal control chromosomes analyzed. GJA8 mutations were seen in two of the 60 unrelated probands with cataracts. Affected individuals in both of whose families also had microcornea and variable myopia.

Conclusions: This is the first report of mutations in GJA8 to be associated with autosomal dominant cataract and microcornea. Mutations in GJA8 cause 3.3% of congenital cataracts in the population of India.