新发现Leber先天性黑矇患者复合杂合突变位点c.1831T>C/c.2172T>A  

Two Compound Heterozygous Variants(c.1831T > C/c.2172T > A)in Leber Congenital Amaurosis

作　　者：徐献群 王陈[1] 吴业勤[1] 黄朱亮 严明[2] 

机构地区：[1]武汉大学中南医院临床基因诊断中心,武汉430071 [2]武汉大学中南医院眼科,武汉430071

出　　处：《微循环学杂志》2016年第4期15-19,F0003,共6页Chinese Journal of Microcirculation

摘　　要：目的:报告一例散发Leber先天性黑矇(LCA)家系的致病基因复合杂合突变位点c.1831T>C/c.2172T>A。方法:收集LCA患儿临床和家系资料,采集该家系成员患儿及其父母外周静脉血,提取基因组DNA,先行目标区域捕获测序筛查已知的眼科遗传病相关基因,再利用生物信息学分析获取候选基因,最后经Sanger法测序验证及对突变位点进行分子生物信息学分析。结果:高通量测序筛查结果证实患儿CRBI基因上存在复合杂合突变(c.1831T>C,p.S611P;c.2172T>A,p.Y724X)。c.2172T>A为无义突变,具有明显的致病性。Anthe_2000软件分析p.S611P突变未引起蛋白二级结构和疏水性明显变化。结论:CRBI基因的复合杂合突变(c.1831T>C,c.2172T>A)可能导致LCA8型的发生。Objective： To report two compound heterozygous variants（c. 1831T〉C/c. 2172T〉A） in a sporadic family with Leber congenital amaurosis （LCA）. Method： The clinical information and family data of a LAC patient was collected. Genomic DNA was extracted from the blood samples of all family members. We developed a panel for targeted exome sequencing of the patient by selecting related genes of inherited retinal disease. Further bioinformatics analyses and Sanger sequencing were done to confirm the candidate variants. In silico analyses, inclu- ding PolyPhen-2, Mutation Taster, multiple sequence alignment and protein molecular secondary structures and hydrophobicity were performed to predict the consequences of each variant identified. Results： After targeted exome sequencing and comprehensive analysis, two compound heterozygous variants （c. 1831T〉C, p. S611P; c. 2172T〉A, p. Y724X） were identified in the CRBI gene which was responsible for causing LCA. The later was a nonsense mutation that was disease^causing obviously. Protein molecular secondary structures and hydrophobicity analysis by Anthe_2000 p. S611P didn＇t show significant change. Conclusion： In this study, two compound heterozygous variants （c. 1831T〉C/c. 2172T〉A） in CRBI that are likely to be the disease-causing variants of LCA 8.

关 键 词：Leber先天性黑矇 CRBI基因复合杂合突变 

分 类 号：Q319.31[生物学—遗传学]