Novel mutations in GJA8 associated with autosomal dominantcongenital cataract and microcornea

[摘要] Purpose: The purpose of this study was to estimate the importance ofmutations in the connexin50 gene (GJA8) as a cause of congenital ordevelopmental cataracts in the Indian population and to identify novelmutations in GJA8 that cause cataract in this population.Methods: The coding region of GJA8 was analyzed for mutation bysingle strand conformational polymorphism in 60 probands affected withcongenital or developmental cataract of which 11 probands' cornealdiameter measured less than 11.00 mm. Direct sequencing was performedfor samples that displayed an abnormal electrophoresis pattern. Thesegregation of the change with the diseased phenotype was analyzed inthe entire pedigree by restriction fragment length polymorphism (RFLP)analysis.Results: Molecular analysis of GJA8 revealed two novel missensemutations V44E and R198Q, in the population screened. The mutationscosegregated with the diseased phenotype in an autosomal dominant mannerand were absent in 400 normal control chromosomes analyzed. GJA8mutations were seen in two of the 60 unrelated probands with cataracts.Affected individuals in both of whose families also had microcornea andvariable myopia.Conclusions: This is the first report of mutations in GJA8 to beassociated with autosomal dominant cataract and microcornea. Mutationsin GJA8 cause 3.3% of congenital cataracts in the population ofIndia.

[学科分类] 生物化学/生物物理