一个甲基丙二酸血症家系的高通量测序鉴别诊断  

Differential diagnosis of a Chinese pedigree with methylmalonic acidemia by next-generation sequencing

作　　者：赵干业 陈晨[1] 赵学潮 刘莉娜 王聪慧 孔祥东[1] Zhao Ganye;Chen Chen;Zhao Xuechao;Liu Lina;Wang Conghui;Kong Xiangdong(Genetics and Prenatal Diagnosis Center,Department of Obstetrics and Gynecology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院妇产医学部遗传与产前诊断中心,郑州450052

出　　处：《中华医学遗传学杂志》2022年第7期694-697,共4页Chinese Journal of Medical Genetics

基　　金：郑州大学第一附属医院院内青年创新基金;河南省科技攻关计划(202102310391);郑州市科技惠民计划(2021KJHM0003)。

摘　　要：目的探讨一例初步诊断疑似丙酸血症的患儿的遗传学病因,对疾病进行精准诊断,为患儿的诊疗及该家系后续遗传咨询提供依据。方法采集患儿外周血后提取基因组DNA,对其甲基丙二酸血症和丙酸血症相关致病基因(MUT、MMACHC、MMAA、MMAB、MMADHC、LMBRD1、PCCA、PCCB和SLC22A5)进行高通量测序,筛查致病变异位点;针对高通量测序未覆盖区域设计引物后进行一代测序;抽取其父母和姐姐的外周血提取基因组DNA后进行变异位点验证。结果患儿MUT基因存在c.1560+2T>C和c.729_730insTT(p.Asp244fs)复合杂合变异,丙酸血症相关基因未发现致病变异。患儿姐姐与父亲携带MUT基因c.1560+2T>C杂合变异;患儿母亲携带MUT基因c.729_730insTT(p.Asp244fs)杂合变异。结论患儿为MUT基因c.729_730insTT(p.Asp244fs)和c.1560+2T>C复合杂合变异所致的甲基丙二酸血症患者,患儿姐姐与患儿父母为携带者;基因检测利于甲基丙二酸血症和丙酸血症的鉴别诊断。Objective To explore the genetic etiology of a child with suspected propionic acidemia.Methods Genomic DNA was extracted from peripheral blood sample of the child and subjected to high-throughput sequencing to screen pathogenic variants of genes associated with methylmalonic acidemia and propionic acidemia,including MUT,MMACHC,MMAA,MMAB,MMADHC,LMBRD1,PCCA,PCCB and SLC22A5.Candidate variants were verified by Sanger sequencing of the proband,her parents and sister.Results The proband was found to harbor two pathogenic variants of the MUT gene,namely c.1560+2T>C and c.729_730insTT(p.Asp244fs),but not in genes associated with propionic acidemia.Her sister and father had carried c.1560+2T>C,and her mother had carried c.729_730insTT(p.Asp244fs).Conclusion The proband was diagnosed as methylmalonic acidemia due to compound heterozygous variants of c.1560+2T>C and c.729_730insTT(p.Asp244fs)of the MUT gene.Her elder sister and parents were all carriers.Genetic testing has facilitated differential diagnosis of methylmalonic acidemia and propionic acidemia in this pedigree.

关 键 词：高通量测序 甲基丙二酸血症 丙酸血症 基因检测 

分 类 号：R725.8[医药卫生—儿科]