利用目标区域捕获测序筛查Leber先天性黑矇的致病基因及其临床表型

目的探讨我国一个散发的Leber先天性黑矇（LCA）家系的致病基因变异位点及其临床表型。方法实验研究。收集嘉兴市妇幼保健院一个散发LCA家系共7名家庭成员的临床资料，其中1名LCA患者，6名正常家属。完善该家系内所有成员的眼科检查，采集该家系成员的外周静脉血，提取基因组DNA，运用目标区域捕获测序技术来筛查患者的283个视网膜疾病相关的基因，测序结果运用生物信息学分析得到候选基因，最后用Sanger测序验证。结果临床检查结果表明患者呈现典型的LCA临床症状。遗传学筛查结果证实患者在NMNAT1基因上存在2个复合杂合变异和1个纯合变异：具体为杂合的错义变异（c.634G>A，p.V212M），杂合的内含子变异（c.-57+7T>G）和纯合的错义变异（c.764G>A，p.S255N）。结论本例患者的NMNAT1基因上存在3个不同的变异，很可能是导致其患有Leber 先天性黑矇的原因。

Targeted exome sequencing identifies NMNAT1 variants in a family with Leber congenital amaurosis

Objective To determine the disease-causing variants in a Chinese family with Leber congenital amaurosis (LCA) and characterize the clinical phenotypes.Methods This research was conducted at the Maternal and Child Health Hospital in Jiaxing and involved a family of which one member was an LCA patient and the other six members were not affected.Genomic DNA was extracted from the blood samples of all family members.We developed a panel for targeted exome sequencing (TES) of family members by selecting 283 known retina-related genes.Further bioinformatics analyses and Sanger sequencing were done to confirm the candidate variants.Results Ophthalmic examination of the patient showed a typical LCA phenotype.After TES and comprehensive analyses,two compound heterozygous variants (c.634G＞A,p.V212M;c.-57+7T＞G) were identified and one homozygous missense (c.764G＞A,p.S255N) in the NMNA T1 gene which is responsible for causing LCA.Conclusion In this study,targeted exome sequencing revealed three variants in NMNA T1 that are likely to be the disease-causing variants of LCA.