Analyses of GATA4, NKX2.5, and TFAP2B genes in subjects from southern China with sporadic congenital heart disease
Analyses of GATA4, NKX2.5, and TFAP2B genes in subjects from southern China with sporadic congenital heart disease
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中国南方散发性先天性心脏病患者 GATA4、NKX2.5 和 TFAP2B 基因分析
DOI：
10.1016/j.carpath.2012.07.001
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发表时间：
2013-03-01
影响因子：
3.7
通讯作者：
Xu, Xiangmin
中科院分区：
文献类型：
--
作者：
Xiong, Fu;Li, Qian;Xu, Xiangmin
背景：先天性心脏病是中国南方新生儿最常见的出生缺陷。 GATA4、NKX2.5 和 TFAP2B 基因的种系突变已被确定与先天性心脏病有关。中国南方先天性心脏病患者中 GATA4、NKX2.5 和 TFAP2B 突变的频率及其基因型与先天性心脏病表型之间的相关性尚不清楚。方法：我们通过变性筛选中国南方 224 名先天性心脏病患者的 GATA4、NKX2.5 和 TFAP2B 基因编码外显子和侧翼内含子序列的种系突变。结果：在 30 名先天性心脏病患者中鉴定出 15 个 GATA4 基因杂合突变，其中包括 1 名室间隔缺损患者中的 GATA4 新型杂合错义突变 (c.788 C>G)。在一名心内膜垫缺损患者中发现了一种新的 TFAP2B 突变（c.31 A>G），在 6 名患有法洛四联症（一名患者）、持续性动脉干（两名患者）和动脉导管未闭（三名患者）的患者中发现了一种未报告的新型 TFAP2B 变异（c.1006 G>A）。除患者中的几个单核苷酸多态性外，未报道NKX2.5突变。结论：这些结果表明基因组GATA4和TFAP2B错义突变可能与中国南方先天性心脏病患者临床表型多样的非家族性先天性心脏病有关。他们还透露，NKX2.5基因的变异可能不是该人群中散发性先天性心脏病患者的危险因素。 Crown 版权所有 (C) 2013 由 Elsevier Inc. 出版。保留所有权利。
Background: Congenital heart disease is the most common birth defect in newborns in southern China. The germline mutations in GATA4, NKX2.5, and TFAP2B genes have been identified to be responsible for congenital heart disease. The frequency of GATA4, NKX2.5, and TFAP2B mutations in subjects with congenital heart disease in southern China and the correlation between their genotype and congenital heart disease phenotype are not known.Methods: We screened germline mutations in the coding exons and the flanking intron sequences of the GATA4, NKX2.5, and TFAP2B genes in 224 congenital heart disease patients located in southern China by denaturing high-performance liquid chromatography and DNA sequencing.Results: Fifteen heterozygous mutations in the GATA4 gene were identified in 30 congenital heart disease patients, including a novel heterozygous missense mutation (c.788 C>G) of GATA4 in one patient with ventricular septal defect. A novel TFAP2B mutation (c.31 A>G) in a patient with endocardial cushion defect and an unreported novel TFAP2B variant (c.1006 G>A) in six patients suffering from tetralogy of Fallot (one patient), persistent truncus arteriosus (two patients) and patent ductus arteriosus (three patients) was found. There were no reported NKX2.5 mutations except for several single nucleotide polymorphisms in the patients.Conclusion: These results suggest that genomic GATA4 and TFAP2B missense mutations may be associated with nonfamilial congenital heart disease with diverse clinical phenotypes in patients with congenital heart disease from southern China. They also revealed that the variation of the NKX2.5 gene may not be a risk factor for sporadic patients with congenital heart disease in this population. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.