NIPBL基因杂合错义变异致德朗热综合征的基因型及表型分析
Phenotypic and molecular characterization of Cornelia de Lange syndrome caused by heterozygous missense variant in the NIPBL gene
阮妙华 1周永海 2王楸 1卢家程 1姜赛芝 1龚雨静 1王丹1
作者信息
- 1. 温州医科大学附属第一医院儿科,浙江温州 325015
- 2. 温州医科大学附属第二医院儿科,浙江温州 325000
- 折叠
摘要
目的 探讨1例NIPBL基因杂合错义变异所致德朗热综合征(CdLS)患儿的临床特点及发病机制.方法 选取2023年7月因"智力障碍及发育迟缓"就诊于温州医科大学附属第一医院的1例疑似CdLS患儿为研究对象.提取患儿及父母外周血中DNA,经全外显子组测序法检测相关变异及Sanger测序法验证变异;用生物信息学对可疑变异进行检测.结果 发现患儿NIPBL基因第42外显子存在c.7168G＞A(p.A2390T)杂合错义变异,该变异为新发变异,且为国内未报道过的新变异.经PolyPhen-2、Mutation Taster、CADD和REVEL软件预测,c.7168G＞A(p.A2390T)变异为可能有害变异.上述变异在ExAC、1000G、dbSNP等数据库中均未见收录,据美国医学遗传学与基因组学学会(ACMG)指南评判为可能致病.结论 结合临床表现,考虑NIPBL基因c.7168G＞A(p.A2390T)错义变异为该家系患儿罹患CdLS综合征的致病原因.基因检测技术可以辅助临床医师确诊CdLS综合征,基因变异检测结果可以为家系的遗传咨询和产前诊断提供依据.
Abstract
Objective To investigate the clinical characteristics and genetic basis of Cornelia de Lange syndrome(CdLS)in a child.Methods The study focused on a proband admitted to the Department of Pediatrics at the First Affiliated Hospital of Wenzhou Medical University in July 2023,presenting with intellectual disability and developmental delay.Ge-nomic DNA was extracted from the proband's peripheral blood sample,and whole-exome sequencing(WES)was performed to identify potential pathogenic variants.The identified variant was further confirmed by Sanger sequencing.Bioinformatic analysis was employed to predict and validate the variant's impact.Results A de novo missense variant,c.7168G＞A(p.A2390T),was identified in the NIPBL gene of the proband.This variant had not been previously reported and was predicted to be pathogenic by multiple prediction tools,including Poly-2,MutationTaster CADD and REVEL.The variant was absent in ma-jor population databases,including ExAC,1000G and dbSNP.Based on the American College of Medical Genetics and Ge-nomics(ACMG)guidelines,the variant was classified as pathogenic.Conclusion The c.7168G＞A(p.A2390T)missense vari-ant is likely responsible for the CdLS in this patient.Genetic testing has been instrumental in diagnosing this condition.
关键词
NIPBL基因/Cornelia/de/Lange综合征/新发变异/错义变异Key words
NIPBL gene/Cornelia de Lange syndrome/de novo variant/missense variant引用本文复制引用
出版年
2024
NETL
NSTL
万方数据