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

[摘要] Purpose: Congenital cataracts are one ofthe most treatable causes of visual impairment and blindness duringinfancy. Approximately 50% of all congenital cataract cases may have agenetic cause. Once there is an intimate relationship betweencrystallin genes and lens transparency, they are excellent candidategenes for inherited cataract. The purpose of this study was toinvestigate mutations in αA-crystallin (CRYAA), γC-crystallin (CRYGC),and γD-crystallin (CRYGD) inBrazilian families with nuclear andlamellar autosomal dominant congenital cataract. Methods: Eleven Brazilian families werereferred to the Santa Casa de São Paulo Ophthalmology Department. Thecoding regions and intron/exon boundaries of CRYAA, CRYGC,and CRYGD were amplified by polymerase chain reaction (PCR) anddirectly sequenced. Mutation screening was performed in the controlgroup by restriction digestion. Results: Two mutations were observed indifferent 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 thenew polymorphism were not observed in the control group. Conclusions: In conclusion, we report anovel nonsense mutation (Y56X) in CRYGD and a previouslyreported missense mutation (R12C) in CRYAA associated withnuclear cataract in Brazilian families. Both tyrosine in amino acid 56in CRYGD and arginine in amino acid 12 in CRYAA havebeen highly conserved throughout evolution in different species. A newpolymorphism (S119S) in CRYGC was also observed in one family.The analysis of nine families excluded possible mutations in thecrystallin genes, suggesting that other genes could be involved withcongenital cataract.

[学科分类] 生物化学/生物物理