Mutational screening of affected cardiac tissues and peripheral blood cells identified novel somatic mutations in GATA4 in patients with ventricular septal defect

Chunyan Cheng, Yuan Lin, Fan Yang, Wenjing Wang, Chong Wu, Jingli Qin, Xiuqin Shao, Lei Zhou

Research output: Contribution to journalArticle

4 Scopus citations


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 ratein cardiac tissues than in peripheral blood cells implies that the genetic contribution to VSD may have been underestimated.

Original languageEnglish (US)
Pages (from-to)425-430
Number of pages6
JournalJournal of Biomedical Research
Issue number6
StatePublished - Nov 1 2011



  • GATA4
  • Somatic mutation
  • Ventricular septal defect

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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