3例CHDFIDD患儿的分子遗传学分析及文献复习  

Molecular genetic analysis of three children with CHDFIDD and literature review

作　　者：赵静 宣小燕 李红英[1] 陈政芳 范晓萱 赵晓科[1] Zhao Jing;Xuan Xiaoyan;Li Hongying;Chen Zhengfang;Fan Xiaoxuan;Zhao Xiaoke(Children’s Hospital of Nanjing Medical University,Nanjing Children’s Hospital,Nanjing 210008,China)

机构地区：[1]南京医科大学附属儿童医院南京儿童医院,南京210008

出　　处：《新医学》2024年第4期292-297,共6页Journal of New Medicine

基　　金：江苏省妇幼保健协会科研基金(FYX202013)。

摘　　要：目的分析先天性心脏缺陷、面部畸形和智力发育障碍[CHDFIDD,细胞周期蛋白依赖性激酶13(CDK13)相关疾病]患儿的临床表型及基因突变情况,探讨其遗传学病因。方法采用芯片捕获高通量测序技术对3例CHDFIDD患儿及其父母的基因组DNA进行全外显子组测序,对疑似致病突变进行Sanger测序验证和生物信息分析。以“CDK13基因”“CDK13相关疾病”为检索词,检索中国知网、万方数据库建库至2024年2月的文献;以“CDK13”“CDK13-related disorder”“CHDFIDD”为检索词,检索PubMed数据库建库至2024年2月的文献,对相关文献进行复习。结果全外显子组测序结果均提示3例患儿存在CDK13基因杂合突变,分别为c.2572C>T(p.Leu858Phe)、c.2579G>A(p.Arg860Gln)和c.2602C>T(p.Arg868Trp),Sanger测序也证实了3种突变,结合临床表型,3例患儿均被确诊为CHDFIDD。3例患儿在各自家系中表现为新发突变;但不排除患儿双亲之一为该突变的生殖系嵌合体。根据美国医学遗传学与基因组学学会的指南,3个突变位点均可能致病。文献复习检索到14篇相关文献共108例CHDFIDD病例,其中c.2572C>T突变未见文献报道。结论CDK13基因突变可能是该3例患儿的遗传学病因。本研究丰富了CDK13基因突变谱,为CHDFIDD相关疾病的诊疗提供了参考。Objective To analyze the clinical and genetic characteristics of three children with congenital heart defects,dysmorphic facial features and intellectual developmental disorders(CHDFIDD).Methods Three children presenting with CHDFIDD were enrolled.Genomic DNA was extracted from peripheral venous blood of the children and their parents.Whole-exome sequencing(WES)was performed using chip-capture high-throughput sequencing technology.Suspected causative mutations were verified by Sanger sequencing and bioinformatic analysis.Using“CDK13 gene”and“CDK13-related diseases”as search terms,literatures of CNKI and Wanfang database were retrieved until February 2024.Using“CDK13”,“CDK13-related disorder”and“CHDFIDD”as search terms,literatures from the establishment of PubMed database untio February 2024 was retrieved,and the relevant literature was reviewed.Results WES revealed heterozygous variants of the CDK13 gene in three children,including c.2572 C>T(p.Leu858Phe),c.2579 G>A(p.Arg860Gln),and c.2602C>T(p.Arg868Trp),which were verified as de novo variants by Sanger sequencing.Combined with the clinical phenotype,all 3 children were diagnosed with CHDFIDD.However,the possibility that one of the affected children’s parents was a germline chimera for the mutation could not be excluded.According to the ACMG guidelines,all three mutation sites were classified as likely pathogenic.A total of 14 studies consisting of 108 cases were retrieved.Among them,c.2572C>T has not been reported.Conclusions The de novo variants of the CDK13 gene may be the genetic cause of developmental delay/intellectual disability in these three children.The findings in the present study expand the spectrum of CDK13 gene mutations,providing reference for the diagnosis of CHDFIDD.

关 键 词：先天性心脏缺陷、面部畸形和智力发育障碍 CDK13基因 CDK13相关疾病 全面性发育迟缓 智力障碍 

分 类 号：R725.4[医药卫生—儿科]