一例德朗热综合征患儿的致病基因变异分析  

Genetic variant analysis of a neonate with Cornelia de Lange syndrome

作　　者：孙媛媛[1] 陈翠娥 狄天伟 邵浩然[1] 朱融和[1] 朱艳可[1] 周爱华[1] 王楸[1] Sun Yuanyuan;Chen Cuie;Di Tianwei;Shao Haoran;Zhu Ronghe;Zhu Yanke;Zhou Aihua;Wang Qiu(Department of Pediatrics,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang 325015,China;Department of Neonatology,Yiwu Maternity and Children Hospital,Jinhua,Zhejiang 322000,China;Department of Pediatrics,Children’s Hospital of Zhejiang University School of Medicine,Hangzhou,Zhejiang 310000,China)

机构地区：[1]温州医科大学附属第一医院儿科,浙江325015 [2]义乌市妇幼保健院新生儿科,浙江322000 [3]浙江大学医学院附属儿童医院新生儿科,杭州310000

出　　处：《中华医学遗传学杂志》2020年第4期449-451,共3页Chinese Journal of Medical Genetics

基　　金：温州市科技局项目(Y20140497)。

摘　　要：目的对1例疑诊德朗热综合征(Cornelia de Lange syndrome,CdLS)的患儿进行致病基因变异检测,明确其发病原因。方法应用高通量捕获测序对CdLS相关致病基因(NIPBL、SMC1A、SMC3、RAD21和HDAC8)进行测序,用Sanger测序验证测序结果以及致病基因的家系分析。结果患儿NIPBL基因存在c.6109-1G>A杂合剪接变异,Sanger测序验证结果表明患儿父母均未携带此变异,提示为新发变异,该变异未在HGMD及ExAC数据库收录。根据Human Splicing Finder预测剪接软件,预测该剪接变异将改变NIPBL基因剪接位点,为致病性变异。未发现SMC1A、SMC3、RAD21和HDAC8基因致病性变异。结论NIPBL基因c.6109-1G>A剪接变异可能是该例患儿的发病原因,新变异的检出丰富了NIPBL基因变异谱。Objective To detect pathogenic variant in a neonate suspected for Cornelia de Lange syndrome(CdLS).Methods Potential mutations of CdLS-related genes(NIPBL,SMC1A,SMC3,RAD21 and HDAC8)were detected by high-throughput target region capture and next-generation sequencing.Suspected variants was verified by Sanger sequencing.Results The child was found to harbor a heterozygous splice site variant,c.6109-1G>A,of the NIPBL gene.Sanger sequencing suggested that neither parent has carried the same variant,suggesting that it was de novo.The variant was unreported by HGMD and ExAC database,and was predicted to alter an acceptor splicing site.No pathogenic variants of SMC1A,SMC3,RAD21 and HDAC8 genes were detected.Conclusion The heterozygous c.6109-1G>A splicing variant of the NIPBL gene may underlie the disease in this child.Above finding has expanded the variant spectrum of the NIPBL gene.

关 键 词：德朗热综合征 NIPBL基因 高通量捕获测序 Sanger测序 

分 类 号：R72[医药卫生—儿科]