应用全外显子测序技术对一个丙酸血症家系进行基因分析及产前诊断  

Analysis of a pedigree affected with propionic acidemia by trio whole exome sequencing

作　　者：阳彦[1] 刘艳秋[1] 陈佳[1] 罗海艳 Yang Yan;Liu Yanqiu;Chen Jia;Luo Haiyan(Prenatal Diagnosis Center of Jiangxi Women and Children’s Health Care Hospital,Nanchang,Jiangxi 330006,China)

机构地区：[1]江西省妇幼保健院产前诊断中心,南昌330006

出　　处：《中华医学遗传学杂志》2020年第7期751-754,共4页Chinese Journal of Medical Genetics

摘　　要：目的探讨1个丙酸血症家系的遗传学病因,为其遗传咨询及产前诊断提供依据。方法应用高通量测序技术对先证者及父母进行核心家系全外显子组测序(whole exome sequencing,WES),用生物信息学软件对变异位点进行致病性分析,并对阳性位点进行Sanger测序验证,检测变异位点是否符合共分离。先证者母亲再次怀孕后于孕18周经羊膜腔穿刺行产前诊断。结果核心家系全WES检测在先证者PCCA基因上检出c.1845+1G>A和c.446delA(p.N149Tfs*35)两个新变异,其父亲携带c.1845+1G>A杂合变异,母亲携带c.446delA杂合变异,先证者二姐遗传来自父亲的c.1845+1G>A变异,胎儿携带c.1845+1G>A杂合变异,出生后随访正常。结论PCCA基因c.1845+1G>A和c.446delA变异是该丙酸血症家系的致病原因,为家系遗传咨询及产前诊断提供了依据。Objective To explore the clinical characteristics and genetic basis for a pedigree affected with propionic acidemia.Methods Trio whole exome sequencing(WES)was used to screen potential variants in the proband and his parents.Sanger sequencing was carried out for the elder sister of the proband,and prenatal diagnosis was carried out at 18th gestational week upon the next pregnancy of his mother.Results Two novel heterozygous variants,PCCA c.1845+1G>A and c.446delA,were detected by WES,for which his father and mother were respectively heterozygous carriers.His elder sister also inherited the PCCA c.1845+1G>A variant from her father,while the fetus was heterozygous for the PCCA c.1845+1G>A variant.Above results were confirmed by Sanger sequencing.Conclusion Identification of the PCCA c.1845+1G>A and c.446delA variants by WES has facilitated genetic counseling and prenatal diagnosis for this family.

关 键 词：丙酸血症 PCCA基因 基因变异 产前诊断 

分 类 号：R596.1[医药卫生—内科学]