新发CHD7基因突变致CHARGE综合征的诊断分析  

Application of targeted next-generation sequencing for syndromic congenital heart defects with novel mutations in CHARGE syndrome

作　　者：吴逊 宋洁 唐幂[1] Wu Xun;Song Jie;Tang Mi(Department of Cardiothoracic Surgery,Second Xiangya Hospital,Central South University,Changsha 410011,China;Department of Cardiovascular Medicine,Second Xiangya Hospital,Central South University,Changsha 410011,China)

机构地区：[1]中南大学湘雅二医院心血管外科,长沙410011 [2]中南大学湘雅二医院心血管内科,长沙410011

出　　处：《临床小儿外科杂志》2022年第9期850-854,共5页Journal of Clinical Pediatric Surgery

基　　金：湖南省自然科学基金(2022JJ30840,2020JJ5831)。

摘　　要：目的分析3例新发CHD7(OMIM#214800)基因突变致CHARGE综合征(PMID:10590394)患儿的临床特点和遗传学特征,探讨靶向测序在CHARGE综合征研究中的应用。方法以中南大学湘雅二医院心血管外科收治的3例综合征型先天性心脏病(简称先心病)患儿为研究对象,采用二代测序技术,结合生物信息学工具对可能产生先天性心血管畸形(特别是综合征型先心病)的445个候选基因进行靶向测序,并采用Sanger测序验证;结合文献和表型分析,确定相关综合征类型。结果通过基于二代测序平台下的靶向测序及筛选,3例患儿均存在新发的CHD7变异:c.G4516A(p.G1506S)、c.A5408G(p.Y1803C)和c.C4894T(p.R1632C)。通过SIFT、PolyPhen 2、MutationTaster软件进行生物信息学分析,其中至少两种判定为致病,提示CHD7变异为致病突变可能性大。结合3例患儿临床表现(包括发育迟缓、智力障碍、语言障碍、精神障碍、特殊面容、骨骼四肢改变、心脏疾病等),与既往报道的CHARGE综合征临床表现高度重合,诊断为CHARGE综合征。结论靶向捕获技术测序能够对综合征型先心病患儿进行快速、准确和全面的检测分析,获取可靠的遗传信息。Objective To analyze the clinical and genetic characteristics of three children with CHARGE syndrome(PMID:10590394)caused by CHD7(OMIM#214800)gene mutation,and to explore the application of targeted sequencing in the study of CHARGE syndrome.Methods Genetic diagnostics were performed using a targeted next-generation sequencing panel of 445 candidate genes.New mutations were confirmed by Sanger sequencing.Three CHARGE syndrome patients were further examined with a brief review of literature.Results Through targeted sequencing and screening based on next-generation sequencing platform,new CHD7 variants were found in all three patients:c.G4516A(p.G1506S),c.A5408G(p.Y1803C)and c.C4894T(p.R1632C).Through SIFT,PolyPhen 2,MutationTaster bioinformatics analysis,at least two of the analysis software identified the pathogenic mutation,indicating that the possibility of pathogenic mutation was high.Combined with the clinical manifestations of the three children,including developmental delay,intellectual disability,language disorder,mental disorder,special facial features,skeletal limb changes,heart disease and other clinical manifestations,the clinical manifestations of CHARGE syndrome were highly consistent with those reported previously,and the diagnosis of CHARGE syndrome could be made.Conclusion Targeted next-generation sequencing enables a rapid and accurate genetic diagnosis in syndromic congenital heart disease.

关 键 词：心脏病/先天性 多位点测序分型 CHARGE综合征/诊断 突变/遗传学 

分 类 号：R725.4[医药卫生—儿科]