Mutation analysis in Chinese families with autosomal dominant hereditary cataracts.

Purpose: To identify the molecular basis and clinical phenotype in three Chinese families with hereditary cataracts.

Methods: Detailed family history and clinical data were recorded. The phenotypes were documented using slit-lamp photography. Candidate genes sequencing was performed to screen out the disease causing mutation. Bioinformatics analysis was performed to predict the function of mutant genes.

Results: The phenotypes of the families were identified as nuclear cataract in Family 1, pulverulent cataract in Family 2, and nuclear cataract in Family 3. Direct sequencing revealed transversions of C > T at c.218 (p. S73F) in GJA8 in Family 1, A > C at c.125 (p. E42A) in GJA3 in Family 2, and C > T at c.268 (p. L90F) in GJA3 in Family 3. These mutations co-segregated with all affected individuals in the family and were not found in unaffected family members nor in the 100 unrelated controls. Bioinformatics analysis indicated that S73F in GJA8, E42A and L90F in GJA3 are highly conserved. S73F in GJA8, E42A and L90F in GJA3 could possibly be damaging predicted by PolyPhen-2, with score of 0.858, 1.000, 1.000, respectively.

Conclusions: This study identified three mutations in three Chinese families with hereditary cataracts. Of the three mutations, two were novel (c.125 A > C in GJA3 and c.268 C > T in GJA3), one was previously reported (c.218 C > T in GJA8).