摘要背景 RP为遗传性致盲眼病,其遗传方式和临床表型呈高度异质性,对患者的突变基因进行筛查和诊断对于进一步的基因治疗研究有重要意义. 目的 利用目标区域捕获技术确定中国一常染色体隐性遗传RP家系成员的临床表型及基因突变方式.方法 收集2013年暨南大学附属深圳眼科医院1个汉族RP家系,对该RP家系的4个成员进行眼科检查,抽取家系成员的外周血后,利用华大基因眼科芯片目标区域捕获技术对先证者进行基因突变检测,利用PCR以及Sanger测序法对RP家系中正常表型的成员进行基因突变点验证. 结果 该家系共3代5名成员,Ⅰ1、Ⅰ2、Ⅱ2和Ⅲ1均为表型正常者,Ⅱ1为先证者,自18岁出现夜盲及视力下降,呈管状视野缺损.先证者眼底检查发现视盘呈蜡黄色和视网膜骨细胞样色素沉积,荧光素血管造影可见片状遮蔽荧光和周边视网膜透见荧光.该家系遗传方式符合常染色体隐性遗传.芯片分析发现先证者USH2A基因存在由c.9958 G＞T(p.Gly3320Cys)错义突变和c.11156 G＞A(p.Arg3719His)错义突变组成的复合杂合突变,而其表型正常的父亲(Ⅰ 1)为c.9958 G＞T(p.Gly3320Cys)杂合突变,表型正常的母亲(Ⅰ 2)为c.11156 G＞A(p.Arg3719His)杂合突变,表型正常的女儿(Ⅲ1)为c.9958 G＞T(p.Gly3320Cys)杂合突变. 结论 该RP家系可能由USH2A基因的c.9958 G＞T和c.11156G＞A复合杂合突变导致.眼科芯片技术可以快速准确地筛查RP常见候选基因.

abstractsBackground RP is the term given to a set of hereditary retinal diseases.RP has groups of clinical characteristics and is a complex disease associated with distinct inheritance patterns.The screening and diagnosis of RP patients is of important significance for the future gene therapy.Objective This study was to characterize the clinical features of a Chinese family with autosomal recessive RP and screen candidate genes.Methods All members of the family underwent complete ophthalmologic examinations.Targeted-capture next generation sequencing (NGS) based molecular genetic analysis was performed on proband to detect mutation.Identified variations were verified in rest family members by PCR and Sanger sequencing.This study was approved by Ethic Committee of Shenzhen Eye Hospital,and written informed consent was obtained from patients prior to any medical examination.Results Proband was diagnosed as RP at 18 years old.His parents and child were asymptomatic.The compound heterozygous mutations in the USH2A gene were identified in the proband,which included c.9958 G ＞T (p.Gly3320Cys) mutation and c.11156 G＞A (p.Arg3719His) mutation.The two mutations were inherited from his unaffected parents,respectively.Conclusions The novel compound heterozygous c.9958 G＞T and c.11156 G＞A mutations of USH2A gene are identified as causative mutations of RP in this family.Targetedcapture NGS based eye disease chip can be vital for detecting known RP genes mutations quickly.Targeted-capture NGS can be a new applicable and efficient method for molecular genetic analysis of ocular disease.