家族性渗出性玻璃体视网膜病变患者TSPAN12基因新突变与表型研究  

Studies on a novel mutation and phenotypes of TSPAN12 gene in patients with familial exudative vitreoretinopathy

作　　者：邹刚[1,2] 綦睿 马美娇 毕小军 王婵娟[1,2] 虎学君 蔡玉娟[1,2] 李慧平[1,2] ZOU Gang;QI Rui;MA Meijiao;BI Xiaojun;WANG Chanjuan;HU Xuejun;CAI Yujuan;LI Huiping(Eye Hospital,People’s Hospital of Ningxia Hui Autonomous Region,Yinchuan 750002,China;The First Affiliated Hospital of Northwest University for Nationalities,Yinchuan 750002,China)

机构地区：[1]宁夏回族自治区人民医院眼科医院,宁夏银川750002 [2]西北民族大学第一附属医院,宁夏银川750002

出　　处：《宁夏医学杂志》2022年第4期299-301,F0003,共4页Ningxia Medical Journal

基　　金：宁夏自然科学基金资助项目(2018AAC03169);宁夏科技厅重点研发计划项目(2020BEG03044);中央高校基础研究基金项目(31920200027)。

摘　　要：目的家族性渗出性玻璃体视网膜病变是一组以视网膜周边血管发育异常为特征的遗传性致盲性眼病,采用二代基因测序技术对8个家族性渗出性玻璃体视网膜病变家系致病基因和临床表型进行研究。方法选取8个FEVR家系成员行详细的眼科检查,采集先证者及家系成员外周静脉血5 mL,提取DNA,应用包含232个致病基因的遗传性视网膜疾病捕获芯片进行靶向捕获富集高通量测序。测序数据利用在线分析软件对可疑基因变异致病性进行预测,确定致病基因及突变位点,利用Sanger测序对先证者及家系成员进行共分离分析。结果共收集8个FEVR家系,临床表型为轻至重度,其中4个家系筛查到致病性突变,1个家系发现FZD4基因的已知突变c.757C>T,突变导致第253位的精氨酸变为半胱氨酸;3个家系检测到TSPAN12突变,占75%,其中1个家系检测到TSPAN12基因的一个新的杂合错义突变:c.633T>A,p.Tyr211Ter突变。突变导致第211位的酪氨酸突变而提前终止转录,患者临床表型较轻。结论此研究鉴定了TSPAN12基因一个新发终止子突变位点p.Tyr211Ter,丰富了TSPAN12基因突变谱,对FEVR遗传分子诊断有一定价值。Objective To study the pathogenic genes and clinical phenotypes of eight families with familial exudative vitreoretinopathy(FEVR)by using the next-generation sequencing(NGS)technology.Methods Detailed ophthalmic examinations were performed on 8 FEVR family members.Peripheral venous blood(5 mL)of probands and family members were collected,and DNA was extracted.A genetic retinal disease capture chip containing 232 pathogenic genes was used for targeted capture enrichment and high-throughput sequencing.Online analysis software was used for sequencing data to predict the pathogenicity of suspected gene variation,and pathogenic genes and mutation sites were determined.Sanger sequencing was used for co-separation analysis of probands and family members.Results The clinical phenotype of 8 FEVR families was mild to severe,and the pathogenic mutations were detected in 4 families.A novel stop codon of TSPAN12,a heterozygous missense mutation NM_012338.4:c.633T>A,NP_036470.1:p.Tyr211Ter involved in highly conserved residues in the proband.Retrospective analysis of its clinical manifestation showed that the mutant carrier presented mild clinical features.Conclusion The novel stop codon mutation p.Tyr211Ter in the TSPAN12 is identitied,which creates a milder phenotype and expands the mutation spectrum of TSPAN12,It would be valuable for future genetic disease diagnosis.

关 键 词：家族性渗出性玻璃体视网膜病变 终止子突变 TSPAN12基因 

分 类 号：R774.1[医药卫生—眼科]