二叶式主动脉瓣畸形相关GATA5基因突变谱分析

doi:10.3969/j.issn.1673-8640.2014.03.008

检验医学 ›› 2014, Vol. 29 ›› Issue (3): 237-240.DOI: 10.3969/j.issn.1673-8640.2014.03.008

• 分子诊断技术的临床应用专题 • 上一篇下一篇

二叶式主动脉瓣畸形相关GATA5基因突变谱分析

徐蕾，袁方，李若谷，王倩，郑洪珍，杨奕清

上海交通大学附属胸科医院心内科，上海 200030

收稿日期:2014-01-09 出版日期:2014-03-30 发布日期:2014-04-19
通讯作者: 杨奕清，联系电话:021-62821990。
作者简介:徐蕾，女，1972年生，硕士，副主任医师，主要研究方向为心血管病的发生机制与干预策略。
基金资助:
国家自然科学基金（81070153，81270161）；国家基础研究计划项目（2010CB912604）

Analysis on mutational spectrum of GATA5 gene associated with bicuspid aortic valve

XU Lei,YUAN Fang,LI Ruogu,WANG Qian,ZHENG Hongzhen,YANG Yiqing.

Department of Cardiology,Shanghai Chest Hospital,Shanghai Jiaotong University,Shanghai 200030,China

Received:2014-01-09 Online:2014-03-30 Published:2014-04-19

摘要/Abstract

摘要：

目的　分析先天性二叶式主动脉瓣畸形(BAV)相关GATA5基因突变谱。方法　收集150例先天性BAV患者和200名健康对照者的临床资料和血标本，使用DNA纯化试剂盒抽提基因组DNA。通过聚合酶链反应扩增GATA5基因的编码区和剪接点，采用双脱氧核苷链末端合成终止法测序，将所测序列与GenBank数据库中的GATA5基因序列进行比对以发现GATA5基因突变。分别应用在线软件MUSCLE和MutationTaster评估突变氨基酸的保守性和致病性。结果　在2例先天性BAV患者各发现1个新的GATA5基因杂合突变，即p.M219I和p.T289I，突变率约为1.33%。这2种突变均不存在于200名健康对照者中。多序列比对显示被改变氨基酸在进化上均完全保守，致病性预测表明这2种突变均具有致病性。结论　发现BAV相关GATA5基因新突变，有助于揭示BAV新的分子机制。

关键词: GATA5基因, 转录因子, 先天性心脏病, 二叶式主动脉瓣畸形, 遗传学

Abstract:

Objective　To analyze the mutational spectrum of GATA5 gene associated with congenital bicuspid aortic valve(BAV). Methods　A total of 150 patients with congenital BAV and a total of 200 healthy subjects as controls were enrolled. The clinical data were collected,and the peripheral venous blood specimens were prepared. The genomic DNA was isolated by DNA purification kit. The coding regions and splice junction sites of GATA5 gene were amplified by polymerase chain reaction,and the amplicons were sequenced by di-deoxynucleotide chain termination technique. The acquired sequences were aligned with those of GATA5 released from GenBank to identify the likely sequence mutations. The online software MUSCLE and MutationTaster were used to evaluate whether the altered amino acids were conserved evolutionarily and whether the mutations were causative,respectively. Results　Two novel heterozygous GATA5 mutations,p.M219I and p.T289I,were identified in 2 congenital BAV patients,respectively,with a mutational prevalence of approximately 1.33%. The 2 mutations,which altered the amino acids completely conserved evolutionarily,were absent in the 200 controls and were both predicted to be pathogenic. Conclusions　This study links novel GATA5 mutations to congenital BAV,which helps to reveal new molecular mechanism underlying congenital BAV.

Key words: GATA5 gene, Transcriptional factor, Congenital heart disease, Bicuspid aortic valve, Genetics

中图分类号:

R446.7

徐蕾，袁方，李若谷，王倩，郑洪珍，杨奕清. 二叶式主动脉瓣畸形相关GATA5基因突变谱分析[J]. 检验医学, 2014, 29(3): 237-240.

XU Lei，YUAN Fang，LI Ruogu，WANG Qian，ZHENG Hongzhen，YANG Yiqing. Analysis on mutational spectrum of GATA5 gene associated with bicuspid aortic valve[J]. , 2014, 29(3): 237-240.

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二叶式主动脉瓣畸形相关GATA5基因突变谱分析

Analysis on mutational spectrum of GATA5 gene associated with bicuspid aortic valve

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