对海南省210例散发性先天性单纯性心脏病患者NKX2-5、GATA4、ZIC3基因突变的筛选研究  

Screening of NKX2-5,GATA4,ZIC3 gene mutations in sporadic congenital simple heart disease in Hainan Province

作　　者：李青蔓 郭丰 凌奕[2] 李慧慧 刘芳芳 刘辉 温壮飞 孙薇薇[5] 刘亦恒[6] 张海英[1] LI Qing-Man;GUO Feng;LING Yi;LI Hui-hui;LIU Fang-fang;LIU Hui;WEN Zhuang-fei;SUN Wei-wei;LIU Yi-heng;ZHANG Hai-ying(Hainan Medical University Key Laboratory for Research and Transformation of Tropical Brain Science,Haikou 571199,China;Department of Obstetrics and Gynecology,The First Affiliated Hospital of Hainan Medical College,Haikou 570102,China;Department of Laboratory,The First Hospital of Nanping City,Fujian Province,Nanping 353006,China;Children's Rehabilitation Department,Haikou Hospital of the Maternal and Child Health,Haikou 570102,China;Department of Pediatrics,Haikou People’s Hospital,Haikou 570208,China;Department of Orthopedics,Haikou Affiliated Hospital of Central South University Xiangya School of Medicine,Haikou 570208,China)

机构地区：[1]海南医学院热带脑科学研究与转化重点实验室,海南海口571199 [2]海南医学院第一附属医院妇产科,海南海口570102 [3]福建省南平市第一医院检验科,福建南平353006 [4]海口市妇幼保健院儿童康复科,海南海口570102 [5]海口市人民医院儿科,海南海口570208 [6]中南大学湘雅医学院附属海口医院骨科,海南海口570208

出　　处：《海南医学院学报》2022年第19期1472-1478,共7页Journal of Hainan Medical University

基　　金：海南省自然科学基金资助项目(821RC562);海南省重研项目(ZDYF2022SHF2081);国家自然科学基金资助项目(81660224);海南省研究生创新课题(Qhys2021-353)。

摘　　要：目的:心脏发育异常可导致先天性心脏病(congenital heart disease,CHD),是国内外最常见的先天性畸形,已知NKX2-5、GATA4和ZIC3基因突变可引起CHD。本实验探讨了海南省NKX2-5、GATA4、ZIC3基因突变和散发性先天性单纯性心脏病之间的关系。方法:收集210例散发性CHD患者,提取患者血液DNA,扩增目的基因片段,利用高分辨熔解曲线(high-resolution melting,HRM)技术和DNA测序技术,分析NKX2-5、GATA4和ZIC3基因的序列。结果:对210例CHD患者NKX2-5、GATA4、ZIC3基因测序,发现7个基因突变,包括1个NKX2-5杂合错义突变(c.178G>T),GATA4的3个杂合突变(c.677C>T,c.928A>G,c.1123G>A),ZIC3的3个杂合突变(c.19G>C,c.1255C>G,c.1348C>T)。其中NKX2-5(c.178G>T)、GATA4(c.1123G>A)、ZIC3(c.19G>C,c.1255C>G,c.1348C>T)为新突变位点。通过生物信息学软件预测这些基因突变为致病性突变。结论:在210例患者中发现了7个基因突变,首次报道海南省NKX2-5、GATA4和ZIC3的基因突变与CHD发病相关。Objective:Congenital heart disease(CHD)is caused by abnormal cardiac development,which is the most common congenital malformation at home and abroad.NKX2-5,GATA4 and ZIC3 have been shown to be associated with CHD.This experiment explored the relationship between NKX2-5,GATA4 and ZIC3 gene mutations and sporadic CHD in Hainan Province.Methods:To collect 210 sporadic CHD patients in Hainan,the DNA of patients was extracted from blood,and the tar‐get gene fragments were amplified.Using high-resolution melting(HRM)and DNA sequencing technology,and we analyzed the sequences of NKX2-5,GATA4 and ZIC3 genes.Results:NKX2-5,GATA4 and ZIC3 genes were sequenced in 210 CHD pa‐tients,and seven gene mutations were found,including NKX2-5 heterozygous missense mutation(c.178G>T)and three hetero‐zygous mutations in GATA4(c.677C>T,c.928A>G,c.1123G>A),three heterozygous mutations in ZIC3(c.19G>C,c.1255C>G,c.1348C>T),in which NKX2-5(c.178G>T),GATA4(c.1123G>A),and ZIC3(c.1255C>G,c.1348C>T)are new mutation sites.These gene mutations were predicted to be pathogenic mutations by bioinformatics software.Conclusion:Conclusion:Seven gene mutations were found in 210 patients,and it was the first report that the gene mutations of NKX2-5,GA⁃TA4 and ZIC3 in Hainan Province associated with the pathogenesis of CHD.

关 键 词：先天性心脏病 基因突变 NKX2-5 GATA4 ZIC3 

分 类 号：R541.1[医药卫生—心血管疾病]