二代测序技术对易误诊为视网膜色素变性的两个中国无脉络膜症家系鉴别诊断  

Diagnosis of choroideremia in two Chinese families misdiagnosed as retinitis pigmentosa using next-generation sequencing

作　　者：王苗苗 王卓实[1] 孙岩 夏阳 何伟[1] Wang Miaomiao;Wang Zhuoshi;Sun Yan;Xia Yang;He Wei(Liaoning He University,Shenyang 110000,China)

机构地区：[1]辽宁何氏医学院,110000

出　　处：《中华实验眼科杂志》2019年第9期719-724,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：辽宁省自然科学基金项目(17-600-9-00)。

摘　　要：目的应用二代测序技术(NGS)鉴别无脉络膜症与视网膜色素变性(RP)。方法采用横断面研究设计。纳入2017年1月至2018年12月在沈阳何氏眼科医院就诊的2个经外院临床医生诊断为RP的家系,采集相关病史资料,询问家族史,并绘制家系图,进行视力、眼压、眼底照相、视网膜电图(ERG)、B型超声、视野、色觉、光相干断层扫描(OCT)、裂隙灯显微镜检查,并进行目标序列捕获测序和Sanger验证,大片段的缺失插入经实时荧光定量PCR检测进行验证。结果识别了CHM基因中的2个已知致病突变EX9 DEL和c.715C>T,明确诊断为无脉络膜症,家系1先证者Ⅱ1携带EX9 DEL半合子突变,双眼黄斑中心凹处可见星型小片完整脉络膜。家系2患者携带c.715C>T致病突变,先证者Ⅲ1为半合子突变,双眼眼底可见黄斑中心凹处淡红色岛区;先证者母亲Ⅱ2和外祖母Ⅰ2为杂合突变,眼底萎缩程度较先证者Ⅲ1轻,眼底呈斑驳样外观,视盘界清色可,血管粗细适中,眼底萎缩区可见暴露的脉络膜。结论本研究首次在亚洲满族和汉族人群中识别了CHM基因EX9 DEL和c.715C>T致病突变,c.715C>T致病突变女性携带者与男性患者临床表型不同。NGS可能成为鉴别无脉络膜症与RP的有力工具。Objective To identify choroideremia and retinitis pigmentosa(RP)using next-generation sequencing(NGS)technology.Methods A cross-sectional study was adopted.The participants were two pedigrees that was suspected of RP in previous hospital treatments in He Eye Specialist Hospital between January 2017 and December 2018.The relevant medical and family history were collected,and the family tree was plotted.The visual acuity,intraocular pressure,fundus photography,electroretinogram(ERG),B-mode ultrasond,visual field,color vision,optical coherence tomography(OCT),and slit lamp assessment were performed on all subjects.Target region sequencing and Sanger sequencing were performed,deletion insertion of large fragments was verified by real-time quantitative PCR.This study followed the Helsinki Declaration and was approved by the Ethics Committee of Shenyang He Eye Hospital(NO.IRB[2017]k002.01)Results Two known pathogenic mutations were identified in CHM gene:EX9 DEL and c.715C>T.Furthermore,the clinical diagnosis of choroideremia was confirmed.The Family 1 probandⅡ1 with the EX9 DEL hemizygous mutation had a special clinical phenotype,“Star”small piece intact choroid was visible in the macular fovea of both eyes.The patients in pedigree 2 carried the pathogenic mutation c.715C>T,the probandⅢ1 carried a hemizygous mutation and the reddish island area in the fovea macula was seen in both eyes.The motherⅡ2 and grandmother I2 of proband carried heterozygous mutations,the degree of fundus atrophy was lighter than that of the probandⅢ1,the fundus had a mottled appearance,the optic disc boundary was clear,the blood vessel thickness was moderate,and the exposed choroid was visible in the fundus atrophy area.Conclusions This study is the first to identify two known pathogenic mutations in CHM gene,EX9 DEL and c.715C>T in Asian Manchu and Han populations.The clinical phenotypes of female carriers with the c.715C>t pathogenic mutation are different from those of male patients.The NGS technology may become a powerful tool

关 键 词：无脉络膜症 突变 二代测序技术 

分 类 号：R73[医药卫生—肿瘤]