GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5

@article{Garg2003GATA4MC,
  title={GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5},
  author={Vidu Garg and Irfan S. Kathiriya and Robert Barnes and Marie K. Schluterman and Isabelle N. King and Cheryl A. Butler and Caryn R. Rothrock and Reenu S. Eapen and Kayoko Hirayama-Yamada and Kunitaka Joo and Rumiko Matsuoka and Jonathan C. Cohen and Deepak Srivastava},
  journal={Nature},
  year={2003},
  volume={424},
  pages={443-447}
}
Congenital heart defects (CHDs) are the most common developmental anomaly and are the leading non-infectious cause of mortality in newborns. Only one causative gene, NKX2-5, has been identified through genetic linkage analysis of pedigrees with non-syndromic CHDs. Here, we show that isolated cardiac septal defects in a large pedigree were linked to chromosome 8p22-23. A heterozygous G296S missense mutation of GATA4, a transcription factor essential for heart formation, was found in all… 
GATA4 mutations in 357 unrelated patients with congenital heart malformation.
TLDR
The spectrum of mutations associated with cardiac septal defects is expanded and two novel putative mutations identified in five patients with atrial or ventricular septals that were not seen in control subjects do not support GATA4 mutations as a common cause of CHD.
Identification of Functional Mutations in GATA4 in Patients with Congenital Heart Disease
TLDR
This study direct sequencing of the GATA4 coding region and exon-intron boundaries in 384 sporadic Chinese CHD patients identified 12 heterozygous non-synonymous mutations, among which 8 mutations were only found inCHD patients when compared with 957 controls, six of which have not been previously reported.
Novel NKX2-5 mutations responsible for congenital heart disease.
TLDR
The spectrum of mutations in NKX2-5 associated with CHD is expanded and new insight is provided into the molecular etiology involved in the pathogenesis of CHD, which signifies potential implications for genetic diagnosis and gene-specific therapy for this common disease in newborns.
Interaction of Gata4 and Gata6 with Tbx5 is critical for normal cardiac development.
TLDR
A genetic interaction between Gata6 and Tbx5 with an incompletely penetrant phenotype of neonatal lethality and thin myocardium is demonstrated, highlighting the unique genetic interactions of Gata4 and Gata 6 with TbX5 for normal cardiac morphogenesis in vivo.
A Novel Missense Mutation of GATA4 in a Chinese Family with Congenital Heart Disease
TLDR
This study identified a novel mutation in GATA4 that likely contributed to the CHD in this family and expanded the spectrum of Gata4 mutations and underscored the pathogenic correlation between GATA 4 mutations and CHD.
Identification of GATA6 Sequence Variants in Patients With Congenital Heart Defects
TLDR
Biochemical studies demonstrate that the GATA 6 A178V mutant protein results in increased transactivation ability when compared with wild-type GATA6, and suggest that nonsynonymous Gata6 sequence variants are infrequently found in individuals with CHD.
Novel GATA6 mutations associated with congenital ventricular septal defect or tetralogy of fallot.
TLDR
In this study, the whole coding region of GATA6, a gene encoding a zinc-finger transcription factor crucial for normal cardiogenesis, was sequenced in 380 unrelated patients with CHD and novel insight is provided into the molecular mechanism implicated in CHD.
Screening and biochemical analysis of GATA4 sequence variations identified in patients with congenital heart disease
TLDR
GATA4 mutations that result in deficits in transactivation ability are consistently associated with CHD suggesting that normal transactivation properties of GATA4 are required for proper cardiac development.
Spectrum of heart disease associated with murine and human GATA4 mutation.
TLDR
The phenotypic spectrum of heterozygous Gata4 mutation in mice is established, and the degree to which GATA4 mutation contributes to human CHD characterized by ECD or RV hypoplasia is determined.
Novel PITX2c loss-of-function mutations associated with complex congenital heart disease.
TLDR
This study demonstrates the association between PITX2c loss-of-function mutations and the transposition of the great arteries and ventricular septal defect in humans, providing further insight into the molecular mechanisms responsible for CHD.
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