先天性白内障家系致病基因筛查及相关生物信息学分析  

Pathogenic Genes and Protein Function Changes in a Congenital Hereditary Cataract Pedigree

作　　者：庄晓彤[1] 肖伟[2] 

机构地区：[1]沈阳市第四人民医院眼科,沈阳110031 [2]中国医科大学附属盛京医院眼科,沈阳110004

出　　处：《中国医科大学学报》2017年第8期673-676,共4页Journal of China Medical University

基　　金：国家自然科学基金(30973276)

摘　　要：目的直接测序检测先天性白内障家系突变,探讨先天性白内障的可能机制。方法收集1个常染色体显性遗传的先天性白内障家系,进行候选基因(CRYGD基因)外显子测序筛查突变后,利用生物数据库分析CRYGD蛋白质野生型及突变型的理化特性以及翻译后的修饰、功能域、二级结构和三级结构等。结果对CRYGD基因直接测序显示,碱基第452位插入GACT4个碱基,发生了移码突变。突变后等电点的变化影响晶状体细胞内的p H值。功能结构域变短,蛋白质内部重复性变化,从而影响蛋白功能。结论发现了CRYGD基因1个新的突变位点—Tyr151X,该突变为首次报道的由插入突变引起先天性白内障的CRYGD基因移码突变。Objective We screened for mutations in an autosomal dominant congenital cataract pedigree by gene sequence analysis to provide a basis for genetic diagnosis of congenital cataract. Methods A Chinese family with congenital nuclear cataract was recruited for mutational screen- ing of candidate genes by direct sequencing. We analyzed the differences between the CRYGD gene mutant and wild-type in terms of protein con- formation and structural domains using bioinformatics methods. Results We detected a novel heterozygous variant c.451_452insGACT in exon 3 of CRYGD. Bioinformatics analysis showed that the mutated CRYGD protein structural domain became shorter, the conformation became simpler, and protein inner repeatability was altered, affecting protein function. Conclusion We found that the Tyr151X gene mutation of CRYGD can lead to congenital hereditary cataract. To date, this is the only detected frameshift mutation caused by an insertion in CRYGD gene mutations.

关 键 词：CRYGD基因 生物信息学 基因突变 先天性白内障 

分 类 号：R774.1[医药卫生—眼科]