CHD7基因变异所致CHARGE综合征1例患儿的临床表型及遗传学分析  

Clinical features and genetic analysis of a case with CHARGE syndrome due to variant of CHD7 gene

作　　者：韩春晓 闫露露[1] 张玉鑫[1] 李海波 Han Chunxiao;Yan Lulu;Zhang Yuxin;Li Haibo(Comprehensive Prevention and Control Center for Birth Defects,Ningbo Women and Children′s Hospital,Ningbo,Zhejiang 315000,China)

机构地区：[1]宁波市妇女儿童医院出生缺陷综合防治中心,宁波315000

出　　处：《中华医学遗传学杂志》2024年第8期962-965,共4页Chinese Journal of Medical Genetics

基　　金：宁波市科技计划(202002N3150);宁波市医疗卫生高端团队项目(20220405);宁波市社会公益项目(2022S035)。

摘　　要：目的对1例CHARGE综合征患儿进行遗传学分析,以明确其致病原因。方法选取2022年9月29日于宁波市妇女儿童医院就诊的1例患儿作为研究对象。收集患儿的临床资料,通过全外显子组测序(WES)分析患儿携带的可疑变异,应用Sanger测序进行家系验证,并对变异进行保守性分析与蛋白结构预测。结果WES检测结果显示患儿携带CHD7基因c.2972T>C(p.L991S)杂合错义变异,其父母均为野生型。根据美国医学遗传学与基因组学学会(ACMG)相关指南,该变异被判定为可能致病性(PM6+PM2_Supporting+PP2+PP3+PP4)。经生物信息学相关软件预测,该变异位点编码的第991位亮氨酸在进化上高度保守,变异型CHD7蛋白(p.L991S)第991位丝氨酸与993位精氨酸之间产生了新的氢键。结论CHD7基因c.2972T>C(p.L991S)杂合错义变异可能为上述CHARGE综合征患儿的致病原因。上述发现丰富了CHARGE综合征CHD7基因的变异谱。ObjectiveTo explore the genetic basis for child with CHARGE syndrome.MethodsA child who was diagnosed at Ningbo Women and Children′s Hospital on September 29,2022 was selected as the study subject.Relevant clinical data were collected.The child and her parents were subjected to whole exome sequencing(WES),and candidate variant was verified by Sanger sequencing and bioinformatic analysis.ResultsThe child was found to harbor a de novo c.2972T>C(p.L991S)missense variant of the CHD7 gene,which was detected in neither of her parents.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the variant was predicted to be likely pathogenic(PM6+PM2_Supporting+PP2+PP3+PP4).Bioinformatic analysis predicted that amino acid 991 is highly conserved among various species,and a hydrogen bond has formed between Asp993 and the mutant Ser991.ConclusionThe heterozygous c.2972T>C(p.L991S)missense variant of the CHD7 gene probably underlay the pathogenesis of CHARGE syndrome in this child.Above finding has also enriched the mutational spectrum for CHARGE syndrome.

关 键 词：CHARGE综合征 CHD7基因 全外显子组测序 

分 类 号：R725.9[医药卫生—儿科]