A novel mutation of GATA4 (K300T) associated with familial atrial septal defect

Gene. 2016 Jan 10;575(2 Pt 2):473-477. doi: 10.1016/j.gene.2015.09.021. Epub 2015 Sep 12.


The GATA-binding protein 4 gene (GATA4) encodes a zinc-finger transcription factor that plays a key role in embryogenesis and cardiac development. Variants in the GATA4 gene have been implicated in several congenital heart diseases (CHD), such as the tetralogy of Fallot (ToF), atrial septal defect (ASD), ventricular septal defect (VSD), atrioventricular septal defect (AVSD), and dilated cardiomyopathy (DCM). We studied a four-generation Chinese ASD family and identified a novel GATA4 mutation (c.A899C, p.K300T) in all surviving affected members and two carriers with incomplete penetrance. Bioinformatics programs (PolyPhen-2, SIFT, and MutationTaster) predicted the mutation to be deleterious. The lysine at the mutation position was highly conserved from Drosophila to humans and was recognized as a methylation location in the GATA4 protein. The involvement of the lysine methylation in cardiogenesis by attenuating the transcriptional activity of GATA4 in mice has been previously examined. Our study broadens the mutation spectrum of the GATA4 gene and reveals for the first time a mutation at the methylation position of GATA4 associated with ASD.

Keywords: Incomplete penetrance; Methylation; Post-translational modification; Ventricular septal defect; Whole exome sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Asian People / genetics*
  • Child
  • China
  • Female
  • GATA4 Transcription Factor / genetics*
  • Genetic Predisposition to Disease
  • Heart Septal Defects, Atrial / genetics*
  • Humans
  • Lysine / metabolism
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Penetrance
  • Sequence Analysis, DNA
  • Young Adult


  • GATA4 Transcription Factor
  • GATA4 protein, human
  • Lysine