TFAP2B基因变异所致Char综合征1例患儿的临床特征及遗传学分析

Clinical characteristics and genetic analysis of a child with Char syndrome caused by TFAP2B gene variant

目的探讨1例Char综合征患儿的临床特征及遗传学病因。方法选取2022年2月就诊于河南省儿童医院儿童保健科的1例Char综合征患儿作为研究对象。收集患儿的临床资料,采集患儿及其父母的外周血样,提取基因组DNA,对患儿进行全外显子组测序,用Sanger测序对候选变异进行家系验证和致病性评定。结果患儿主要表现为特殊面容、动脉导管未闭、全面发育迟缓、小拇指、脚中趾弯曲,全外显子组测序显示其携带TFAP2B基因c.944A>C(p.Glu315Ala)杂合变异。Sanger测序显示其父母未携带相同的变异。根据美国医学遗传学和基因组学学会(ACMG)相关指南,该变异被判定为可能致病性(PM1+PM2_Supporting+PM6+PP3)。结论TFAP2B基因c.944A>C(p.Glu315Ala)杂合变异可能是上述Char综合征患儿的遗传学病因。新变异的检出拓宽了TFAP2B基因的变异谱和临床表型谱,有助于临床对Char综合征的早期识别与诊断。

ObjectiveTo explore the clinical features and genetic etiology of a child with Char syndrome.MethodsA child who was presented at the Department of Child Health,Henan Children′s Hospital in February 2022 was selected as the study subject.Clinical data of the child was collected,and peripheral blood samples of the child and her parents were collected for the extraction of genomic DNA.Whole exome sequencing was carried out,and candidate variants were verified by Sanger sequencing and bioinformatic analysis.ResultsThe child had mainly manifested facial dysmorphism,patent ductus arteriosus,growth retardation,curving of fifth fingers and middle toes.Whole exome sequencing revealed that she has harbored a heterozygous c.944A>C(p.Glu315Ala)variant of the TFAP2B gene,which was verified to be de novo by Sanger sequencing.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was rated to be likely pathogenic(PM1+PM2_Supporting+PM6+PP3).ConclusionThe heterozygous c.944A>C(p.Glu315Ala)variant of the TFAP2B gene probably underlay the Char syndrome in this child.Above finding has expanded the mutational and phenotypic spectra of the TFAP2B gene,which has facilitated early identification and diagnosis of Char syndrome.