Somatic mutations in the GATA6 gene underlie sporadic tetralogy of Fallot

  • Authors:
    • Ri-Tai Huang
    • Song Xue
    • Ying-Jia Xu
    • Yi-Qing Yang
  • View Affiliations

  • Published online on: November 20, 2012     https://doi.org/10.3892/ijmm.2012.1188
  • Pages: 51-58
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Abstract

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease associated with significant morbidity and mortality in humans. However, the molecular etiology underlying TOF in most patients remains largely unknown. In the present study, sequence analysis of the GATA6 gene was performed from fresh-frozen cardiac tissues and matched blood samples of 52 unrelated patients who underwent surgical repair of TOF. The cardiac tissues and matched blood specimens from 46 patients who underwent cardiac valve replacement due to rheumatic heart disease and blood samples from 200 healthy individuals as controls were genotyped. The functional characteristics of the mutations were assessed using a luciferase reporter assay system. Based on the results, two novel heterozygous GATA6 mutations, p.G367X and p.G394C, were identified in the cardiac tissues of 2 TOF patients, respectively. No mutations were found in the cardiac tissues from 46 patients with rheumatic heart disease and in the blood samples from the 298 participants. Functional analysis demonstrated that the GATA6 mutants were consistently associated with significantly reduced transcriptional activation compared with their wild-type counterpart. This is the first report on the link of somatic GATA6 mutation to TOF, providing novel insight into the molecular mechanism involved in TOF.
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January 2013
Volume 31 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Huang R, Xue S, Xu Y and Yang Y: Somatic mutations in the GATA6 gene underlie sporadic tetralogy of Fallot. Int J Mol Med 31: 51-58, 2013.
APA
Huang, R., Xue, S., Xu, Y., & Yang, Y. (2013). Somatic mutations in the GATA6 gene underlie sporadic tetralogy of Fallot. International Journal of Molecular Medicine, 31, 51-58. https://doi.org/10.3892/ijmm.2012.1188
MLA
Huang, R., Xue, S., Xu, Y., Yang, Y."Somatic mutations in the GATA6 gene underlie sporadic tetralogy of Fallot". International Journal of Molecular Medicine 31.1 (2013): 51-58.
Chicago
Huang, R., Xue, S., Xu, Y., Yang, Y."Somatic mutations in the GATA6 gene underlie sporadic tetralogy of Fallot". International Journal of Molecular Medicine 31, no. 1 (2013): 51-58. https://doi.org/10.3892/ijmm.2012.1188