Mutation analysis of CRYAA, CRYGC, and CRYGD associated with autosomal dominant congenital cataract in Brazilian families

PURPOSE: Congenital cataracts are one of the most treatable causes of visual impairment and blindness during infancy. Approximately 50% of all congenital cataract cases may have a genetic cause. Once there is an intimate relationship between crystallin genes and lens transparency, they are excellent candidate genes for inherited cataract. The purpose of this study was to investigate mutations in αA-crystallin (CRYAA), γC-crystallin (CRYGC), and γD-crystallin (CRYGD) in Brazilian families with nuclear and lamellar autosomal dominant congenital cataract. METHODS: Eleven Brazilian families were referred to the Santa Casa de São Paulo Ophthalmology Department. The coding regions and intron/exon boundaries of CRYAA, CRYGC, and CRYGD were amplified by polymerase chain reaction (PCR) and directly sequenced. Mutation screening was performed in the control group by restriction digestion. RESULTS: Two mutations were observed in different families (Family 4 and Family 10), one is a new mutation (Y56X) in CRYGD and the other a previously reported mutation (R12C) in CRYAA that is correlated with a different phenotype. Genetic analysis revealed previously described polymorphisms in CRYAA (D2D) and CRYGD (Y17Y and R95R). A new polymorphism in CRYGC (S119S) was identified only in Family 1. The mutations as well as the new polymorphism were not observed in the control group. CONCLUSIONS: In conclusion, we report a novel nonsense mutation (Y56X) in CRYGD and a previously reported missense mutation (R12C) in CRYAA associated with nuclear cataract in Brazilian families. Both tyrosine in amino acid 56 in CRYGD and arginine in amino acid 12 in CRYAA have been highly conserved throughout evolution in different species. A new polymorphism (S119S) in CRYGC was also observed in one family. The analysis of nine families excluded possible mutations in the crystallin genes, suggesting that other genes could be involved with congenital cataract.