TNNI3与TAZ基因变异所致罕见心脏病一个家系的研究  

Analysis of a Chinese pedigree affected with rare heart diseases due to variants of TNNI3 and TAZ genes

作　　者：徐惠玲 胡锐 江璇 雷钏 黄俞龙 王萍 李雪梅[1] Xu Huiling;Hu Rui;Jiang Xuan;Lei Chuan;Huang Yulong;Wang Ping;Li Xuemei(Department of Reproductive Medicine,Shenzhen Maternity and Child Health Care Hospital Affiliated to Southern Medical University,Shenzhen,Guangdong 518048,China)

机构地区：[1]南方医科大学附属深圳市妇幼保健院生殖医学中心,深圳518048

出　　处：《中华医学遗传学杂志》2023年第10期1246-1251,共6页Chinese Journal of Medical Genetics

摘　　要：目的鉴定1例罕见心脏病家系(Barth综合征以及肥原性心肌病)的遗传学病因,为该家系提供遗传咨询及生育指导。方法选取2021年7月9日于南方医科大学附属深圳市妇幼保健院就诊的1个罕见心脏病家系作为研究对象。收集家系成员的临床资料,对患儿及其父母进行家系全外显子组测序(Trio-WES),对家系其他成员进行Sanger测序验证,对变异进行生物学信息分析。参照美国医学遗传学与基因组学学会(ACMG)相关指南判断变异的致病性。结果Trio-WES检测显示先证者携带TAZ基因c.542G>A(p.G181A)半合子变异,该变异遗传自其母亲;此外,其母亲还携带TNNI3基因c.557G>A(p.R186Q)变异。经Sanger测序验证,先证者姨母与外祖母同样携带该变异。参照ACMG相关指南,TAZ基因c.542G>A(p.G181A)评定为可能致病性变异(PS2_Strong+PM2_Supporting+PP3),TNNI3基因c.557G>A(p.R186Q)评定为致病性变异(PP1_Strong+PS4_Strong+PP3+PP4+PM2_Supporting)。结论TAZ基因c.542G>A(p.G181A)可能是先证者患Barth综合征的遗传学病因,TNNI3基因c.557G>A(p.R186Q)变异可能为先证者母亲、姨母及外祖母患肥厚型心肌病的遗传学病因。上述发现拓展了TAZ基因的变异谱,为该家系的临床诊断提供了参考。Objective To explore the genetic basis for a Chinese pedigree affected with rare type heart disease.Methods A pedigree identified at Shenzhen Maternity and Child Health Care Hospital Affiliated to Southern Medical University on July 9,2021 was selected as the study subject.Clinical data were collected.Trio-whole exome sequencing(WES)was carried out for the proband and his parents.Candidate variants were validated by Sanger sequencing of his family members and bioinformatic analysis.Results The proband,a 5-month-old male,was found to have Barth syndrome(dilated myocardiopathy and left ventricular non-compaction).Trio-WES revealed that he has harbored a hemizygous c.542G>A(p.G181A)variant of the TAZ gene,which was inherited from his mother.In addition,his mother,aunt and maternal grandmother were also found to harbor a c.557G>A(p.R186Q)variant of the TNNI3 gene.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the c.542G>A(p.G181A)variant of the TAZ gene was classified as likely pathogenic(PS2_Strong+PM2_Supporting+PP3),whilst the c.557G>A(p.R186Q)variant of the TNNI3 gene was classified as pathogenic(PP1_Strong+PS4_Strong+PP3+PP4+PM2_Supporting).Conclusion The c.542G>A(p.G181A)variant of the TAZ gene probably underlay the Barth syndrome in the proband,and the c.557G>A(p.R186Q)variant of the TNNI3 gene may be responsible for the hypertrophic cardiomyopathy in his mother,aunt and maternal grandmother.Above finding has expanded the mutational spectrum of the TAZ gene and facilitated the diagnosis of this pedigree.

关 键 词：TNNI3基因 TAZ基因 Barth综合征 肥厚型心肌病 

分 类 号：R725.9[医药卫生—儿科]