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Article

A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy

  • Authors:
    • Lan Zhao
    • Jia-Hong Xu
    • Wen-Jun Xu
    • Hong Yu
    • Qian Wang
    • Hong-Zhen Zheng
    • Wei-Feng Jiang
    • Jin-Fa Jiang
    • Yi-Qing Yang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Yantaishan Hospital, Yantai, Shandong 264001, P.R. China, Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China, Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China
  • Pages: 654-660
    |
    Published online on: December 23, 2013
       https://doi.org/10.3892/ijmm.2013.1600
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Abstract

Dilated cardiomyopathy (DCM) is the most common form of primary myocardial disorder and is associated with substantial morbidity and mortality. Increasing evidence suggests that genetic risk factors play an important role in the pathogenesis of idiopathic DCM. However, DCM is a genetically heterogeneous disease, and the genetic defects responsible for DCM in an overwhelming majority of cases remain to be identified. In the present study, the entire coding region and the splice junction sites of the GATA4 gene, which encodes a cardiac transcription factor essential for cardiogenesis, were sequenced in 150 unrelated patients with idiopathic DCM. The available relatives of the index patient harboring an identified mutation and 200 unrelated ethnically matched healthy individuals used as controls were genotyped. The functional characteristics of the mutant GATA4 were delineated in contrast to its wild-type counterpart using a luciferase reporter assay system. As a result, a novel heterozygous GATA4 mutation, p.V291L, was identified in a family with DCM inherited in an autosomal dominant pattern, which co-segregated with DCM in the family with complete penetrance. The missense mutation was absent in 400 control chromosomes, and the altered amino acid was completely conserved evolutionarily among species. Functional analysis revealed that the GATA4 mutant was associated with significantly diminished transcriptional activity. The findings expand the mutational spectrum of GATA4 linked to DCM and provide novel insight into the molecular etiology involved in DCM, suggesting the potential implications in the early prophylaxis and allele-specific treatment for this common type of cardiomyopathy.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao L, Xu J, Xu W, Yu H, Wang Q, Zheng H, Jiang W, Jiang J and Yang Y: A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy. Int J Mol Med 33: 654-660, 2014.
APA
Zhao, L., Xu, J., Xu, W., Yu, H., Wang, Q., Zheng, H. ... Yang, Y. (2014). A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy. International Journal of Molecular Medicine, 33, 654-660. https://doi.org/10.3892/ijmm.2013.1600
MLA
Zhao, L., Xu, J., Xu, W., Yu, H., Wang, Q., Zheng, H., Jiang, W., Jiang, J., Yang, Y."A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy". International Journal of Molecular Medicine 33.3 (2014): 654-660.
Chicago
Zhao, L., Xu, J., Xu, W., Yu, H., Wang, Q., Zheng, H., Jiang, W., Jiang, J., Yang, Y."A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy". International Journal of Molecular Medicine 33, no. 3 (2014): 654-660. https://doi.org/10.3892/ijmm.2013.1600
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao L, Xu J, Xu W, Yu H, Wang Q, Zheng H, Jiang W, Jiang J and Yang Y: A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy. Int J Mol Med 33: 654-660, 2014.
APA
Zhao, L., Xu, J., Xu, W., Yu, H., Wang, Q., Zheng, H. ... Yang, Y. (2014). A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy. International Journal of Molecular Medicine, 33, 654-660. https://doi.org/10.3892/ijmm.2013.1600
MLA
Zhao, L., Xu, J., Xu, W., Yu, H., Wang, Q., Zheng, H., Jiang, W., Jiang, J., Yang, Y."A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy". International Journal of Molecular Medicine 33.3 (2014): 654-660.
Chicago
Zhao, L., Xu, J., Xu, W., Yu, H., Wang, Q., Zheng, H., Jiang, W., Jiang, J., Yang, Y."A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy". International Journal of Molecular Medicine 33, no. 3 (2014): 654-660. https://doi.org/10.3892/ijmm.2013.1600
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