3例CHDFIDD患儿的分子遗传学分析及文献复习OACSTPCD

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.