一个中国汉族X连锁视网膜色素变性家系的RPGR基因突变  

A mutation of the RPGR gene in an X‐linked retinitis pigmentosa family of Chinese Han nationality

作　　者：赵悦 张进 王陈[1] 靳冰玉 梁宾 张晓康 向阳 郑芳[1] ZHAO Yue;ZHANG Jin;WANG Chen;JIN Bingyu;LIANG Bin;ZHANG Xiaokang;XIANG Yang;ZHENG Fang(Center of Gene Diagnosis,Zhongnan Hospital of Wuhan University,Wuhan 430071,Hubei,China;Dept.of Ophthalmology,Jingzhou Maternal and Child Health Care Hospital,Jingzhou 434020,Hubei,China)

机构地区：[1]武汉大学中南医院基因诊断中心,湖北武汉430071 [2]荆州妇幼保健院眼科,湖北荆州434020

出　　处：《武汉大学学报（医学版）》2022年第6期1001-1006,共6页Medical Journal of Wuhan University

摘　　要：目的:在一个具有特殊表型的X连锁色素性视网膜炎(XLRP)家系中确定致病基因并为该家系的遗传咨询提供依据。方法:收集一例诊断为视网膜色素变性的先证者及其家系的临床资料并进行眼部检查,对有条件采集外周静脉血的家系成员采集其外周静脉血,提取基因组DNA。用全外显子组测序(WES)的方法筛选出先证者的潜在致病基因位点,用Sanger测序法对变异位点进行验证随后用遗传学数据库和相关文献等资料对突变位点进行分析。同时对先证者的女儿进行X染色体失活模式检测。结果:全外显子测序和Sanger测序结果共同显示先证者存在RPGR g.ORF15+673_674delAG(p.E809fs)的缺失突变,通过查阅数据库、文献等资料,发现该突变未在中国人群中报道过。该突变会导致氨基酸翻译的提前终止,从而导致蛋白产物的截短,引起相应的疾病。女性携带者(先证者的女儿)的X染色体失活模式为偏斜失活。结论:本研究证实了一个在中国汉族家系报道的RPGR基因突变g.ORF15+673_674delAG(p.E809fs),该突变不仅会导致男性患者有严重的视网膜色素变性(RP)表型,还会导致女性携带者表现出从轻微到严重症状的广泛临床特征。Objective:To identify the causative gene in an X⁃linked retinitis pigmentosa(XLRP)family with a special phenotype and to provide a basis for genetic counseling in this family.Methods:The clinical data of a proband diagnosed as retinitis pigmentosa and his family were collected,and ocular examina⁃tions were performed.Peripheral venous blood was collected from available family members,and ge⁃nomic DNA was extracted.The potential pathogenic gene loci of the proband were screened out by whole exome sequencing(WES),and the mutation sites were verified by Sanger sequencing.Then the mutation sites were analyzed by searching genetic databases and related literature.The pattern of X chromosome inactivation(XCI)was determined for the daughter of the proband.Results:A dele⁃tion mutation of RPGR g.ORF15+673_674delAG(p.E809fs)in the proband was identified by WES and Sanger sequencing.It was found that the mutation had not been reported in the Chinese popula⁃tion by referring to databases,literature and other materials.This mutation would lead to premature termination of amino acid translation,resulting in truncation of protein products and related diseases.The XCI pattern in female carrier(daughter of the proband)is skewed inactivation.Conclusion:This study confirmed a mutation of the RPGR gene g.ORF15+673_674delAG(p.E809fs)reported for the first time in a Chinese Han family,which not only causes a severe retinitis pigmentosa(RP)pheno⁃type in male patients,but also causes a wide range of clinical features ranging from mild to severe symptoms in female carriers.

关 键 词：RPGR基因 基因突变 视网膜色素变性 全外显子测序 X染色体失活 中国 

分 类 号：R774.13[医药卫生—眼科]