A novel mutation in γD-crystallin associated with autosomal dominant congenital cataract in a Chinese family

[摘要] Purpose: To identify the pathogenic genemutation in a Chinese family with autosomal dominant congenital nuclearcataract. Methods: After obtaining informedconsent, detailed ophthalmic examinations were performed and genomicDNAs were obtained from eleven family members in a three-generationChinese family with five affected. All exons of candidate genesassociated with congenital nuclear cataract were amplified bypolymerase chain reaction (PCR) and the PCR products were sequenced inboth directions. The hydrophobic property of the mutant protein wasanalyzed with bioinformatics program ProtScale. The structure homologymodeling of the mutant protein was based on Swiss-Model Serve, and itsstructure was displayed and compared with native γD-crystallin (CRYGD)using the RasMol software. Results: By sequencing the encodingregions of the candidate genes, a novel mutation (c.110G>C) wasdetected in exon 2 of CRYGD, which resulted in the substitutionof a highly conserved arginine by proline at codon 36 (p.R36P). Themutation co-segregated with all patients and was absent in 100 normalChinese controls. Bioinformatics analysis showed an obvious increase ofthe local hydrophilicity of the R36P mutant γD-crystallin. The homologymodeling showed that the structure of the mutant protein was similarwith that of native human γD-crystallin. Conclusions: The study identified anovel mutation (c. 110G>C) in CRYGD associated withautosomal dominant congenital cataract in a Chinese family. It expandsthe mutation spectrum of CRYGD in association with congenitalcataract.

[学科分类] 生物化学/生物物理