GATA5 loss-of-function mutation in familial dilated cardiomyopathy

  • Authors:
    • Xian-Ling Zhang
    • Neng Dai
    • Kai Tang
    • Yan-Qing Chen
    • Wei Chen
    • Juan Wang
    • Cui-Mei Zhao
    • Fang Yuan
    • Xing-Biao Qiu
    • Xin-Kai Qu
    • Yi-Qing Yang
    • Ya-Wei Xu
  • View Affiliations

  • Published online on: December 29, 2014     https://doi.org/10.3892/ijmm.2014.2050
  • Pages: 763-770
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Abstract

Dilated cardiomyopathy (DCM), the most common form of primary myocardial disease, is an important cause of sudden cardiac death and heart failure and is the leading indication for heart transplantation in children and adults worldwide. Recent studies have revealed a strong genetic basis for idiopathic DCM, with many distinct genes causally implicated. Nevertheless, DCM is a genetically heterogeneous disorder and the genetic determinants underlying DCM in a substantial proportion of patients remain unclear. In this study, the whole coding exons and flanking introns of the GATA binding protein 5 (GATA5) gene, which codes for a zinc-finger transcription factor essential for cardiovascular development and structural remodeling, were sequenced in 130 unrelated patients with idiopathic DCM. The available relatives of the index patient carrying an identified mutation and 200 unrelated ethnically matched healthy individuals used as the controls were genotyped for GATA5. The functional characteristics of the mutant GATA5 were analyzed in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system. As a result, a novel heterozygous GATA5 mutation, p.G240D, 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 reference chromosomes and the altered amino acid was completely conserved evolutionarily across species. Functional analyses revealed that the GATA5 mutant was associated with significantly diminished transcriptional activity. This study firstly links GATA5 mutation to DCM, which provides novel insight into the molecular mechanisms of DCM, suggesting a potential molecular target for the prenatal prophylaxis and allele-specific treatment of DCM.
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March-2015
Volume 35 Issue 3

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

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Spandidos Publications style
Zhang X, Dai N, Tang K, Chen Y, Chen W, Wang J, Zhao C, Yuan F, Qiu X, Qu X, Qu X, et al: GATA5 loss-of-function mutation in familial dilated cardiomyopathy. Int J Mol Med 35: 763-770, 2015
APA
Zhang, X., Dai, N., Tang, K., Chen, Y., Chen, W., Wang, J. ... Xu, Y. (2015). GATA5 loss-of-function mutation in familial dilated cardiomyopathy. International Journal of Molecular Medicine, 35, 763-770. https://doi.org/10.3892/ijmm.2014.2050
MLA
Zhang, X., Dai, N., Tang, K., Chen, Y., Chen, W., Wang, J., Zhao, C., Yuan, F., Qiu, X., Qu, X., Yang, Y., Xu, Y."GATA5 loss-of-function mutation in familial dilated cardiomyopathy". International Journal of Molecular Medicine 35.3 (2015): 763-770.
Chicago
Zhang, X., Dai, N., Tang, K., Chen, Y., Chen, W., Wang, J., Zhao, C., Yuan, F., Qiu, X., Qu, X., Yang, Y., Xu, Y."GATA5 loss-of-function mutation in familial dilated cardiomyopathy". International Journal of Molecular Medicine 35, no. 3 (2015): 763-770. https://doi.org/10.3892/ijmm.2014.2050