一例肉碱棕榈酰转移酶1A缺乏症患儿的临床特征和基因变异分析  

Clinical features and genetic variants of a case with carnitine palmitoyltransferase 1A deficiency

作　　者：洪冬洋 王彦云[1] 孙云[1] 马定远[1] 程威[1] 蒋涛[1] Hong Dongyang;Wang Yanyun;Sun Yun;Ma Dingyuan;Cheng Wei;Jiang Tao(Genetic Medicine Center,Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University(Nanjing Maternal and Child Health Hospital),Nanjing,Jiangsu 210004,China)

机构地区：[1]南京医科大学附属妇产医院(南京市妇幼保健院)遗传医学中心,南京210004

出　　处：《中华医学遗传学杂志》2022年第7期739-742,共4页Chinese Journal of Medical Genetics

摘　　要：目的对1例肉碱棕榈酰转移酶1A(carnitine palmitoyltransferase 1A,CPT1A)缺乏症患儿进行基因变异分析,明确其可能的致病原因。方法应用基于Ion Torrent半导体测序技术的遗传代谢病基因诊断Panel进行检测,基因变异以Sanger测序法验证。结果基因测序结果显示患儿CPT1A基因存在c.1895T>A(p.Leu632X)和c.1153G>A(p.Ala385Thr)复合杂合变异,父亲携带c.1895T>A杂合变异,母亲携带c.1153G>A杂合变异。经查询人类基因突变数据库HGMD、遗传病变异数据库ClinVar及文献资料,均为未报道过的新变异。根据美国医学遗传学与基因组学学会遗传变异分类标准与指南,c.1895T>A判定为致病性变异(PVS1+PM2+PP4),c.1153G>A判定为可能致病变异(PM1+PM2+PM3+PP3)。结论CPT1A基因c.1895T>A和c.1153G>A复合杂合变异可能是患儿的致病原因,基因检测结果为其临床诊断和遗传咨询提供了依据,新变异的检出拓展了CPT1缺乏症的基因变异谱。Objective To identify the possible pathogenesis of a neonate with carnitine palmitoyltransferase 1A(CPT1A)deficiency by analyzing genetic variants.Methods Potential variants were detected with an Ion Torrent semiconductor sequencer using a gene panel for inherited diseases,and candidate variants were verified by Sanger sequencing.Results Genetic testing indicated that the neonate has carried c.1895T>A(p.Leu632X)and c.1153G>A(p.Ala385Thr)compound heterozygous variants of the CPT1A gene,which were inherited from his father and mother,respectively.Both variants were verified as novel through the retrieval of HGMD database,ClinVar database and literature.According to the standards and guidelines of the American College of Medical Genetics and Genomics,the c.1895T>A variant was predicted as pathogenic(PVS1+PM2+PP4)and c.1153G>A as likely pathogenic(PM1+PM2+PM3+PP3).Conclusion The c.1895T>A and c.1153G>A compound heterozygous variants of the CPT1A gene might underlie the pathogenesis in this child.Above results have provided a basis for clinical diagnosis and genetic counseling,and enriched the variant spectrum of the CPT1 deficiency.

关 键 词：肉碱棕榈酰转移酶1A缺乏症 串联质谱 CPT1A基因 基因变异 

分 类 号：R725.9[医药卫生—儿科]