COL4A3基因2个新无义变异致Alport综合征的临床和遗传分析  

Clinical and genetic analysis of Alport syndrome caused by two new nonsense variations of COL4A3 gene

作　　者：陈冲 付荣 樊姣姣 和俊杰 陈秋芳 王淑静 王利伟 余自华[3] CHEN Chong;FU Rong;FAN Jiao-jiao;HE Jun-jie;CHEN Qiu-fang;WANG Shu-jing;WANG Li-wei;YU Zi-hua(Department of Pediatrics,Xinxiang Medical University Affiliated Puyang Oilfield General Hospital,Puyang,Henan 457001;Department of Nephrology,Xinxiang Medical University Affiliated Puyang Oilfield General Hospital,Puyang,Henan 457001;Department of Nephrology,Fujian Childrens Hospital,Affiliated Hospital of Fujian Medical University,Fuzhou,Fujian 350014,China)

机构地区：[1]新乡医学院附属濮阳市油田总医院儿科,河南淮阳457001 [2]新乡医学院附属濮阳市油田总医院肾内科,河南濮阳457001 [3]福建医科大学附属福建省儿童医院肾内科,福建福州350014

出　　处：《热带医学杂志》2021年第9期1091-1095,共5页Journal of Tropical Medicine

基　　金：国家自然科学基金(81270766);河南省科技攻关计划项目(102102310100);河南省科技发展计划项目(152102310020);国家卫生健康委科学研究基金河南省医学科技攻关计划省部共建项目(SBGJ202002130)。

摘　　要：目的探讨COL4A3基因突变所引起的常染色体隐性遗传Alport综合征的临床特点和基因变异特点。方法用基因测序和生物信息学分析方法分析1个常染色体隐性遗传Alport综合征患者的临床表型和基因型。结果男性患者,14岁发现水肿、肉眼血尿、蛋白尿、低蛋白血症伴有听力障碍,治疗、随访不规律,20岁进展至终末期肾病。应用全外显子组测序发现COL4A3基因2个新的无义变异,40号外显子上c.3508G>T(p.G1170X)杂合变异,51号外显子上c.4825C>T(p.R1609X)杂合变异,Sanger测序验证患者母亲携带c.3508G>T(p.G1170X)杂合变异,父亲携带c.4825C>T(p.R1609X);患者的哥哥未携带这2个基因变异。这2个无义变异均导致蛋白质表达提前终止,系致病变异。结论COL4A3基因无义变异导致的常染色体隐性Alport综合征在青少年时期进展至终末期肾病;新发现2个COL4A3基因的无义变异;全外显子基因测序是确诊Alport综合征的重要手段。Objective To explore the clinical and genectic variation characteristics of autosomal recessive Alport syndrome caused by COL4A3 gene mutation.Method The clinical phenotype and genotype of a patient with autosomal recessive Alport syndrome were analyzed.Results A 14-year-old boy with edema,gross hematuria,hypoproteinemia,proteinuria and hearing impairment was selected as the research subject.The treatment and follow-up were irregular,and the patient progressed to end-stage renal disease at 20 years old.Two novel nonsense mutations were found by whole exome sequencing,c.3508G>T(p.G1170X)in exon 40 and c.4825C>T(p.R1609X)in exon 51.Sanger sequencing confirmed that the mutation of c.3508G>T(p.G1170X)was inherited from his mother,and the mutation of c.4825C>T(p.R1609X)from his father.The child’s brother did not carry these two gene mutations.Both of these two nonsense mutations lead to the early termination of protein expression,which were pathogenic mutations.Conclusions Autosomal recessive Alport syndrome caused by nonsense mutation of COL4A3 gene progressed to end-stage renal disease in adolescence.Two nonsense mutations of COL4A3 gene were newly discovered by whole exon sequencing,which could be an important method for the diagnosis of Alport syndrome.

关 键 词：ALPORT综合征 COL4A3基因 常染色体隐性遗传 无义变异 终末期肾病 

分 类 号：R692.9[医药卫生—泌尿科学]