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 ...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.展开更多
High degree atrioventricular block （HDAVB） is a serious complication of transcatheter closure of a perimembranous ventricular septal defect （PMVSD）. We report one patient who developed transient HDAVB seven days a...High degree atrioventricular block （HDAVB） is a serious complication of transcatheter closure of a perimembranous ventricular septal defect （PMVSD）. We report one patient who developed transient HDAVB seven days after transcathter closure of PMVSD and had recurrent HDAVB 42 months after the procedure.展开更多
基金supported by National Natural Science Fund of China (No.30871079)National Science Foundation of Jiangsu province (No. BK2007232)
文摘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.
文摘High degree atrioventricular block （HDAVB） is a serious complication of transcatheter closure of a perimembranous ventricular septal defect （PMVSD）. We report one patient who developed transient HDAVB seven days after transcathter closure of PMVSD and had recurrent HDAVB 42 months after the procedure.
