Mutational screening of affected cardiac tissues and peripheral blood cells identified novel somatic mutations in GA TA4 in patients with ventricular septal defect
Chunyan Cheng
Yuan Lin
Fan Yang
Wenjing Wang
Chong Wu
Jingli Qin
Xiuqin Shao
Lei Zhou
摘要：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.
机标关键词：ventricular septal defectGATA4novelblood cellsVSDmutation rateterminationanalysis
分类号：Q78(基因工程（遗传工程）)
资助基金：National Natural Science Fund of China(30871079)National Science Foundation of Jiangsu province(BK2007232)
论文发表日期：2011-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
英文信息