先天性室间隔缺损相关HAND1基因新突变的识别及功能

Identification and functional analysis of a novel HAND1 mutation associated with congenital ventricular septal defect

目的:检测先天性室间隔缺损(ventricular septal defect,VSD)相关HAND1基因新突变并分析其功能。方法:采集125例先天性VSD患者和210名对照者的临床资料和血标本,抽提基因组DNA,扩增HAND1基因的全部编码外显子,并对扩增的基因片段进行测序以识别HAND1基因突变。利用双荧光报告基因分析系统分析突变型HAND1的功能特点。结果:在1例散发性VSD患者中发现了1个新的HAND1杂合突变c.355G>T,亦即E119X突变,该无义突变在210名对照者中并不存在,功能分析显示突变型HAND1丧失了转录、激活靶基因的功能。结论:本研究检测出了一个VSD相关的HAND1基因新突变。

Objective： To identify the novel HAND1 mutation associated with congenital ventricular septal defect（VSD） and to perform the functional analysis.Methods： A total of 125 patients with congenital VSD and 210 control individuals were recruited,and their clinical data and blood samples were collected. The genomic DNA from each study subject was isolated, and all the coding exons of HAND1 were amplified. The amplicons from HAND1 were sequenced to identify a sequence variation. The functional characteristics of the mutant HAND1 were analyzed by a dual-luciferase reporter assay system.Results： A novel heterozygous HAND1 mutation c.355 GT, equivalent to E119 X, was identifiedin a patient with sporadic VSD. This nonsense mutation was absent in the 210 control subjects.Functional analysis revealed that the mutant HAND1 lost the ability to transactivate a target gene.Conclusion： A novel HAND1 mutation with VSD is identified in this study.