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Article

A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation

  • Authors:
    • Xin-Hua Wang
    • Cong-Xin Huang
    • Qian Wang
    • Ruo-Gu Li
    • Ying-Jia Xu
    • Xu Liu
    • Wei-Yi Fang
    • Yi-Qing Yang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Departments of Cardiology and Cardiovascular Research, Shanghai Chest Hospital, Medical College of Shanghai Jiaotong University, Shanghai 200030, P.R. China
  • Pages: 43-50
    |
    Published online on: November 20, 2012
       https://doi.org/10.3892/ijmm.2012.1189
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Abstract

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with significantly increased morbidity and mortality. Cumulative evidence highlights the importance of genetic defects in the pathogenesis of AF. However, AF is of remarkable heterogeneity and the genetic determinants of AF in a vast majority of patients remain illusive. In this study, the coding exons and splice junctions of the GATA5 gene, which encodes a zinc-finger transcription factor essential for normal cardiogenesis, were sequenced in 118 unrelated patients with lone AF. The available relatives of the index patient carrying an identified mutation and 200 unrelated ethnically-matched healthy individuals used as controls were genotyped. The functional effect of the mutant GATA5 was characterized in contrast to its wild-type counterpart using a luciferase reporter assay system. As a result, a novel heterozygous GATA5 mutation, p.W200G, was identified in a family with AF inherited as an autosomal dominant trait. The mutation was absent in 200 control individuals and the altered amino acid was completely conserved evolutionarily across species. Functional analysis showed that the mutation of GATA5 was associated with a significantly decreased transcriptional activity. These findings provide novel insight into the molecular mechanism involved in AF, suggesting potential implications for the early prophylaxis and gene-specific therapy of AF.
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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Huang C, Wang Q, Li R, Xu Y, Liu X, Fang W and Yang Y: A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation. Int J Mol Med 31: 43-50, 2013.
APA
Wang, X., Huang, C., Wang, Q., Li, R., Xu, Y., Liu, X. ... Yang, Y. (2013). A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation. International Journal of Molecular Medicine, 31, 43-50. https://doi.org/10.3892/ijmm.2012.1189
MLA
Wang, X., Huang, C., Wang, Q., Li, R., Xu, Y., Liu, X., Fang, W., Yang, Y."A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation". International Journal of Molecular Medicine 31.1 (2013): 43-50.
Chicago
Wang, X., Huang, C., Wang, Q., Li, R., Xu, Y., Liu, X., Fang, W., Yang, Y."A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation". International Journal of Molecular Medicine 31, no. 1 (2013): 43-50. https://doi.org/10.3892/ijmm.2012.1189
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Huang C, Wang Q, Li R, Xu Y, Liu X, Fang W and Yang Y: A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation. Int J Mol Med 31: 43-50, 2013.
APA
Wang, X., Huang, C., Wang, Q., Li, R., Xu, Y., Liu, X. ... Yang, Y. (2013). A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation. International Journal of Molecular Medicine, 31, 43-50. https://doi.org/10.3892/ijmm.2012.1189
MLA
Wang, X., Huang, C., Wang, Q., Li, R., Xu, Y., Liu, X., Fang, W., Yang, Y."A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation". International Journal of Molecular Medicine 31.1 (2013): 43-50.
Chicago
Wang, X., Huang, C., Wang, Q., Li, R., Xu, Y., Liu, X., Fang, W., Yang, Y."A novel GATA5 loss-of-function mutation underlies lone atrial fibrillation". International Journal of Molecular Medicine 31, no. 1 (2013): 43-50. https://doi.org/10.3892/ijmm.2012.1189
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