Ⅱ型Usher综合征或39型视网膜色素变性患者的临床表型、致病基因与新突变位点分析  

Analysis of clinical phenotypes,pathogenic gene,and novel mutation site in patients with typeⅡUsher syndrome or type 39 retinitis pigmentosa

作　　者：杨极 邹悦[1] 韦春玲[1] 肖丽波[1] 焦康为 YANG Ji;ZOU Yue;WEI Chunling;XIAO Libo;JIAO Kangwei(The Second People’s Hospital of Yunnan Province,Affiliated Hospital of Yunnan University,Yunnan Eye Hospital,Yunnan Clinical Medical Research Center of Eye Diseases,Yunnan Clinical Medical Center of Eye Diseases,Kunming 650000,Yunnan Province,China)

机构地区：[1]云南省第二人民医院,云南大学附属医院,云南省眼科医院,云南省眼部疾病临床医学研究中心,云南省眼病临床医学中心,云南省昆明市650000

出　　处：《眼科新进展》2020年第12期1135-1138,共4页Recent Advances in Ophthalmology

基　　金：国家自然科学基金资助(编号81960180);云南省应用基础研究计划项目(编号2019FB093、2018FB123);云南省科技厅-昆明医科大学应用基础研究联合专项重点项目[编号2018FE001(-008)];云南省卫生科技计划项目(编号2017NS130);云南省科技计划项目重大科技专项(编号2018ZF009)。

摘　　要：目的观察Ⅱ型Usher综合征(USH2)或39型视网膜色素变性患者的临床表型,分析患者的致病基因与新突变位点。方法收集临床诊断为USH2或39型视网膜色素变性患者的相关资料和样本,进行全外显子测序,对测序结果进行分析后锁定致病基因与突变位点,并用Sanger测序验证其突变位点。结果本研究共收集5例患者,来自于3个不同家系,测序数据解读结果显示USH2A基因为5例患者的致病基因,在USH2A基因上共检出3个纯合突变。先证者1(F1-Ⅱ1)及其患病的弟弟(F1-Ⅱ2)在USH2A基因上均存在c.8232G>C(p.W2744C)(M1)纯合突变。先证者2(F2-Ⅱ1)和其患病的妹妹(F2-Ⅱ2)则在USH2A基因上均存在c.8559-2A>G(M2)纯合突变。先证者3(F3-Ⅱ1)在USH2A基因上发现c.12778C>T(p.Q4260X)(M3)纯合突变。其中所发现的M3突变为首次报道。结论USH2A基因突变是导致USH2和39型视网膜色素变性的主要致病原因,USH2A基因突变所致疾病具有典型的遗传异质性和临床异质性,不同的突变所致疾病表型存在差异。Objective To observe the clinical phenotypes of Usher syndrome typeⅡ(USH2)or type 39 retinitis pigmentosa(RP),and to identify the pathogenic genes and mutation sites of the patients by whole exon sequencing.Methods The relevant data of patients with clinical diagnosis of USH2,RP were collected,and whole exon sequencing was performed,as well as the pathogenic genes and mutation sites were identified,and finally the mutation sites were verified by Sanger sequencing.Results A total of 5 patients were collected from 3 different families.The results of sequencing data showed that the USH2A gene was the pathogenic gene in 5 patients,and 3 homozygous mutations were detected on the USH2A gene.c.8232G>C(p.W2744C)(M1)homozygous mutation existed in USH2A gene of proband 1(F1-Ⅱ1)and his affected brother(F1-Ⅱ1).Proband 2(F2-Ⅱ1)and his sister(F2-Ⅱ2)had c.8559-2A>G(M2)homozygous mutation.Proband 3(F2-Ⅱ1)found c.12778C>T(p.Q4260X)(M3)homozygous mutation.The M3 mutation was first reported.Conclusion The mutation of USH2A gene is the main cause of USH2 and type 39 RP.The disease causes by the mutation of USH2A gene has typical genetic heterogeneity and clinical heterogeneity.The phenotypes of diseases cause by different mutations are different.

关 键 词：Ⅱ型Usher综合征 视网膜色素变性 全外显子测序 突变位点 

分 类 号：R774[医药卫生—眼科]