Open Access

Somatic GATA4 mutation contributes to tetralogy of Fallot

  • Authors:
    • Pradhan Abhinav
    • Yan-Jie Li
    • Ri-Tai Huang
    • Xing-Yuan Liu
    • Jia-Ning Gu
    • Chen-Xi Yang
    • Ying-Jia Xu
    • Juan Wang
    • Yi-Qing Yang
  • View Affiliations

  • Published online on: January 8, 2024     https://doi.org/10.3892/etm.2024.12379
  • Article Number: 91
  • Copyright: © Abhinav et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tetralogy of Fallot (TOF) is the most prevalent cyanotic congenital heart pathology and causes infant morbidity and mortality worldwide. GATA‑binding protein 4 (GATA4) serves as a pivotal transcriptional factor for embryonic cardiogenesis and germline GATA4 mutations are causally linked to TOF. However, the effects of somatic GATA4 mutations on the pathogenesis of TOF remain to be ascertained. In the present study, sequencing assay of GATA4 was performed utilizing genomic DNA derived from resected heart tissue specimens as well as matched peripheral blood specimens of 62 patients with non‑familial TOF who underwent surgical treatment for TOF. Sequencing of GATA4 was also performed using the heart tissue specimens as well as matched peripheral venous blood samples of 68 sporadic cases who underwent heart valve displacement because of rheumatic heart disorder and the peripheral venous whole blood samples of 216 healthy subjects. The function of the mutant was explored by dual‑luciferase activity analysis. Consequently, a new GATA4 mutation, NM_002052.5:c.708T>G;p.(Tyr236*), was found in the heart tissue of one patient with TOF. No mutation was detected in the heart tissue of the 68 cases suffering from rheumatic heart disorder or in the venous blood samples of all 346 individuals. GATA4 mutant failed to transactivate its target gene, myosin heavy chain 6. Additionally, this mutation nullified the synergistic transactivation between GATA4 and T‑box transcription factor 5 or NK2 homeobox 5, two genes causative for TOF. Somatic GATA4 mutation predisposes TOF, highlighting the significant contribution of somatic variations to the molecular pathogenesis underpinning TOF.
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February-2024
Volume 27 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Abhinav P, Li Y, Huang R, Liu X, Gu J, Yang C, Xu Y, Wang J and Yang Y: Somatic <em>GATA4</em> mutation contributes to tetralogy of Fallot. Exp Ther Med 27: 91, 2024
APA
Abhinav, P., Li, Y., Huang, R., Liu, X., Gu, J., Yang, C. ... Yang, Y. (2024). Somatic <em>GATA4</em> mutation contributes to tetralogy of Fallot. Experimental and Therapeutic Medicine, 27, 91. https://doi.org/10.3892/etm.2024.12379
MLA
Abhinav, P., Li, Y., Huang, R., Liu, X., Gu, J., Yang, C., Xu, Y., Wang, J., Yang, Y."Somatic <em>GATA4</em> mutation contributes to tetralogy of Fallot". Experimental and Therapeutic Medicine 27.2 (2024): 91.
Chicago
Abhinav, P., Li, Y., Huang, R., Liu, X., Gu, J., Yang, C., Xu, Y., Wang, J., Yang, Y."Somatic <em>GATA4</em> mutation contributes to tetralogy of Fallot". Experimental and Therapeutic Medicine 27, no. 2 (2024): 91. https://doi.org/10.3892/etm.2024.12379