Mutational screening of affected cardiac tissues and peripheral blood cells identified novel somatic mutations in GATA4 in patients with ventricular septal defect.
Mutational screening of affected cardiac tissues and peripheral blood cells identified novel somatic mutations in GATA4 in patients with ventricular septal defect.
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DOI：
10.1016/s1674-8301(11)60056-0
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发表时间：
2011-11
影响因子：
2.3
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Cheng C;Lin Y;Yang F;Wang W;Wu C;Qin J;Shao X;Zhou L
本研究的目的是探讨GATA 4基因体细胞突变如何导致室间隔缺损（VSD）的发生。对20例经手术治疗的VSD先证者的外周血和心脏组织DNA进行了GATA 4编码区和内含子-外显子边界区的测序。在VSD患者的心脏组织中检测到7种新的杂合变异，但在VSD患者的外周血细胞或500例健康对照样本中未检测到。我们复制了NCBI中报道的14个单核苷酸多态性（SNPs）。进行生物信息学分析以分析突变与VSD相关的可能机制。在这些变体中，C。1004 C>A（p.S335X）发生在GATA 4的高度保守结构域并产生终止密码子，这导致产生截短的GATA 4。7个新的杂合GATA 4突变仅在VSD的心脏组织中发现，表明它们是体细胞起源的。心脏组织中的突变率高于外周血细胞，这意味着遗传因素对VSD的影响可能被低估了。
The aim of this study was to examine how somatic mutations of the GATA4 gene contributed to the genesis of ventricular septal defect (VSD). The coding and intron-exon boundary regions of GATA4 were sequenced of DNA samples from peripheral blood cells and cardiac tissues of twenty surgically treated probands with VSD. Seven novel heterozygous variants were detected in cardiac tissues from VSD patients, but they were not detected in the peripheral blood cells of VSD patients or in 500 healthy control samples. We replicated 14 single nucleotide polymorphisms (SNPs) reported in NCBI. Bioinformatics analysis was performed to analyze the possible mechanism by which mutations were linked to VSD. Among those variants, c. 1004C>A (p.S335X) occurred in the highly conserved domain of GATA4 and generated a termination codon, which led to the production of truncated GATA4. The seven novel heterozygous GATA4 mutations were only identified in cardiac tissues with VSD, suggesting that they are of somatic origin. A higher mutation rate in cardiac tissues than in peripheral blood cells implies that the genetic contribution to VSD may have been underestimated.