特发性扩张型心肌病相关GATA6基因新突变的识别  

Identification of a novel GATA6 mutation associated with idiopathic dilated cardiomyopathy

作　　者：李文昭 徐迎佳[1] 李若谷[1] 曲新凯[1] 杨奕清[1] 仇兴标[1] LI Wenzhao;XU Yingjia;LI Ruogu;QU Xinkai;YANG Yiqing;QIU Xingbiao(Department of Cardiology,Shanghai Chest Hospital,Shanghai Jiao Tong University,Shanghai 200030,China)

机构地区：[1]上海交通大学附属胸科医院心内科,200030

出　　处：《国际心血管病杂志》2018年第5期288-291,共4页International Journal of Cardiovascular Disease

基　　金：国家自然科学基金(81470372)

摘　　要：目的:识别特发性扩张型心肌病(DCM)相关GATA6基因新突变。方法:入选132例特发性DCM患者和220名健康对照者,收集其临床资料和外周静脉血,使用DNA纯化试剂盒抽提基因组DNA,采用聚合酶链反应试剂扩增GATA6基因的整个编码区,应用循环测序试剂盒对扩增的GATA6基因片段进行测序,将所测序列与Nucleotide数据库中的GATA6基因序列进行对比分析以识别GATA6基因突变。应用MUSCLE和MutationTaste在线系统评估突变氨基酸进化上的保守性和突变的致病性。结果:通过序列分析发现1例散发性DCM患者的GATA6基因新变异c.1165G>T,相当于p.E389X突变,在220名健康对照者中没有检测出该无义突变。跨物种GATA6蛋白序列比对分析表明,被改变的氨基酸在物种进化上完全保守,致病性预测显示该GATA6基因突变具有致病性。结论:发现散发性DCM相关GATA6基因新突变,扩大了DCM相关GATA6基因突变谱。Objective：To identify a novel GATA6 mutation associated with idiopathic dilated cardiomyopathy（DCM）. Methods：In the present study,132 unrelated cases with idiopathic DCM and220 unrelated healthy control individuals were recruited.The clinical data and the peripheral venous blood samples were collected.The genomic DNA was isolated with a DNA purification kit.The entire coding regions of the GATA6 gene were amplified by using polymerase chain reaction reagents and the amplified GATA6 fragments were sequenced with a cycle sequencing kit.The obtained sequences were aligned with those of GATA6 derived from the Nucleotide database to identify a GATA6 sequence variation.The online computer softwares of MUSCL and MutationTaster were used to evaluate whether the mutated amino acid was conserved evolutionarily and whether the mutation was causative respectively. Results：A novel heterozygous GATA6 mutation c.1165 G〉C,equivalent to p.E389 X,was identified in a sporadic DCM patient.The nonsense mutation was absent in the 220 control subjects.The altered amino acid was highly conserved evolutionarily,and the mutation was predicted to be pathogenic. Conclusions：This study reported the association of a novel GATA6 mutation with sporadic DCM,expanding the mutational spectrum of GATA6 linked to DCM.

关 键 词：扩张型心肌病 分子遗传学 转录因子 GATA6 突变 

分 类 号：R542.2[医药卫生—心血管疾病]