一例3-甲基戊烯二酸尿症Ⅶ型患儿的CLPB基因变异分析  

CLPB gene mutations analysis in a case of type Ⅶ 3-methylglutaconic aciduria

作　　者：董睿 张开慧 黄艳 蒋岳 律玉强 高敏 盖中涛 刘毅 Dong Rui;Zhang Kaihui;Huang Yan;Jiang Yue;Lyu Yuqiang;Gao Min;Gai Zhongtao;Liu Yi(Institute of Pediatric Research,Qilu Children’s Hospital of Shandong University,Jinan,Shandong 250022,China;Physiatry Department,Qilu Children’s Hospital of Shandong University,Jinan,Shandong 250022,China)

机构地区：[1]山东大学齐鲁儿童医院儿科研究所,济南250022 [2]山东大学齐鲁儿童医院康复科,济南250022

出　　处：《中华医学遗传学杂志》2020年第9期1014-1017,共4页Chinese Journal of Medical Genetics

摘　　要：目的对1例临床疑为3-甲基戊烯二酸(3-methylglutaconic acid,3-MGA)尿症的患儿的CLPB基因进行变异分析,为临床诊断提供依据。方法应用高通量测序进行基因检测,对疑似致病性变异进行Sanger测序验证及生物信息学分析。结果基因测序结果显示患儿CLPB基因存在c.1085G>A(p.Arg362Gln)和c.1700A>C(p.Tyr567Ser)复合杂合变异,患儿母亲携带CLPB基因c.1700A>C(p.Tyr567Ser)杂合变异,父亲携带CLPB基因c.1085G>A(p.Arg362Gln)杂合变异,患儿的两个变异位点分别遗传自父亲和母亲。c.1085G>A(p.Arg362Gln)是未报道过的新变异,按照美国医学遗传学会指南评价为可能致病的变异。结论CLPB基因c.1085G>A(p.Arg362Gln)和c.1700A>C(p.Tyr567Ser)复合杂合变异可能为患儿的致病原因,基因测序分析可以明确诊断。Objective To validate the diagnosis of an infant with elevated urine 3-methylglutaconic acid(3-MGA)through sequencing of the CLPB gene.Methods Genomic DNA of the infant was sequenced by next generation sequencing(NGS),and candidate pathogenic variants were verified by Sanger sequencing and bioinformatics analysis.Results NGS has revealed that the infant has carried a c.1085G>A(p.Arg362Gln)and a c.1700A>C(p.Tyr567Ser)of the CLPB gene,which were respectively inherited from her parents.Among these,c.1085G>A(p.Arg362Gln)is a novel variant which was unreported previously,and based on the ACMG guidelines,it was predicted to be a possible pathogenic variant.Conclusion Compound heterozygous variants c.1085G>A(p.Arg362Gln)and c.1700A>C(p.Tyr567Ser)of the CLPB gene probably underlay the disease in this infant.Genetic testing has confirmed the diagnosis.

关 键 词：3-甲基戊烯二酸尿症Ⅶ型 CLPB基因 尿气象色谱串联质谱 3-甲基戊烯二酸 

分 类 号：R725.9[医药卫生—儿科]