先天性白内障致病基因EPHA2的筛查与鉴定  

Screening and Identification of EPHA2 Gene in Congenital Cataract

作　　者：李乾 杨振菲 常亮[3] LI Qian(National Research Institute for Family Planning,Beijing 100081,China)

机构地区：[1]国家卫生计生委科学技术研究所国家人类遗传资源中心,北京100081 [2]国家康复辅具研究中心附属康复医院眼科,北京100176 [3]北京大学第三医院妇产科生殖医学中心,北京100191

出　　处：《河北医学》2018年第8期1245-1249,共5页Hebei Medicine

基　　金：中央公益科研院所基本科研业务经费;(编号:2016GJM05);北京大学第三医院种子基金;(编号:Y83480-01)

摘　　要：目的:应用新一代高通量测序技术研究一个连续三代都有患病的先天性白内障家系的致病基因。方法:采用已知候选基因靶向捕获富集的方法并结合二代测序技术,筛选出候选突变,应用Sanger测序对其进行验证及家系内的共分离检验,之后对其进行信息学预测。结果:该家系共七名患者,遗传方式符合常染色体显性遗传规律。靶向基因测序发现了EPHA2基因的一个杂合突变c.1532C>T,该变异造成EPHA2基因编码的跨膜蛋白受体氨基酸序列错义改变(p.T511M),信息学预测表明E-PHA2氨基酸511位在物种进化上保守且T511M突变引起蛋白质功能改变,Sanger测序结果表明该突变可信并且在先天性白内障家系内与疾病表型共分离。结论:EPHA2基因c.1532C>T(p.T511M)可能是本研究先天性白内障家系的致病突变。病基因。方法:采用已知候选基因靶向捕获富集的方法并结合二代测序技术,筛选出候选突变,应用Sanger测序对其进行验证及家系内的共分离检验,之后对其进行信息学预测。结果:该家系共七名患者,遗传方式符合常染色体显性遗传规律。靶向基因测序发现了EPHA2基因的一个杂合突变c.1532C>T,该变异造成EPHA2基因编码的跨膜蛋白受体氨基酸序列错义改变(p.T511M),信息学预测表明EPHA2氨基酸511位在物种进化上保守且T511M突变引起蛋白质功能改变,Sanger测序结果表明该突变可信并且在先天性白内障家系内与疾病表型共分离。结论:EPHA2基因c.1532C>T(p.T511M)可能是本研究先天性白内障家系的致病突变。Objective： To investigate the pathogenesis gene in a family with autosomal dominant congenital cataracts（ADCC） by target rejoin capture sequencing. Methods： A three-generations Chinese family with ADCC were recruited and all patients underwent comprehensive ophthalmic examinations. Target rejoin capture sequencing was performed on the proband,then the sequencing results were compared with the data of human genomic database,the synonymous mutation was filled after reported common variants. Sanger sequencing was used to validate co-segregation of the candidate variant in the family. The impact on the amino acid sequences and the conservation of the variant were further analyzed. Results： Seven patients were found in this family,the patients were distributed in each generation with equal incidence rates in male and female subjects.Target rejoin capture sequencing found a heterozygous mutation c. 1532 C T（p. T511 M） in EPHA2（ephrin type A receptor2）,which was highly conserved among various species and resulted in an abnormal EPHA2 protein. Then the Sanger sequencing showed co-segregation of the mutation in the family. Conclusion： EPHA2 gene c.1532 CT（p.T511 M） may be a pathogenic mutation in the family of congenital cataract.

关 键 词：先天性白内障 靶向捕获高通量测序 EPHA2 突变 

分 类 号：R776.1[医药卫生—眼科]