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Article

Novel GATA6 loss-of-function mutation responsible for familial atrial fibrillation

  • Authors:
    • Jian Li
    • Wei-Dong Liu
    • Zhong-Liang Yang
    • Yi-Qing Yang
  • View Affiliations / Copyright

    Affiliations: Department of Emergency, Pu Nan Hospital, Shanghai 200125, P.R. China, Department of Neurosurgery, Pu Nan Hospital, Shanghai 200125, P.R. China, Department of Cardiovascular Research, Shanghai Chest Hospital, Medical College of Shanghai Jiaotong University, Shanghai 200030, P.R. China
  • Pages: 783-790
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    Published online on: July 18, 2012
       https://doi.org/10.3892/ijmm.2012.1068
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Abstract

Atrial fibrillation (AF) is the most commonly sustained cardiac arrhythmia, and confers a substantially increased risk of morbidity and mortality. Increasing evidence has indicated that hereditary defects are implicated in AF. However, AF is genetically heterogeneous and the genetic etiology of AF in a significant portion of patients remains unclear. In this study, the entire coding sequence and splice junctions of the GATA6 gene, which encodes a zinc-finger transcription factor crucial for cardiogenesis, were sequenced in 140 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 the controls were genotyped. The functional characteristics of the mutant GATA6 were assessed in contrast to its wild-type counterpart using a luciferase reporter assay system. As a result, a novel heterozygous GATA6 mutation, p.G469V, was identified in a family with AF inherited in an autosomal dominant pattern. The mutation was absent in the 200 control individuals and the altered amino acid was completely conserved across species. Functional analysis demonstrated that the GATA6 mutation was associated with a significantly decreased transcriptional activity. The findings provide novel insight into the molecular mechanism involved in the pathogenesis of AF, as well as insight into potential therapies for the prevention and treatment of AF.
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Copy and paste a formatted citation
Spandidos Publications style
Li J, Liu W, Yang Z and Yang Y: Novel GATA6 loss-of-function mutation responsible for familial atrial fibrillation. Int J Mol Med 30: 783-790, 2012.
APA
Li, J., Liu, W., Yang, Z., & Yang, Y. (2012). Novel GATA6 loss-of-function mutation responsible for familial atrial fibrillation. International Journal of Molecular Medicine, 30, 783-790. https://doi.org/10.3892/ijmm.2012.1068
MLA
Li, J., Liu, W., Yang, Z., Yang, Y."Novel GATA6 loss-of-function mutation responsible for familial atrial fibrillation". International Journal of Molecular Medicine 30.4 (2012): 783-790.
Chicago
Li, J., Liu, W., Yang, Z., Yang, Y."Novel GATA6 loss-of-function mutation responsible for familial atrial fibrillation". International Journal of Molecular Medicine 30, no. 4 (2012): 783-790. https://doi.org/10.3892/ijmm.2012.1068
Copy and paste a formatted citation
x
Spandidos Publications style
Li J, Liu W, Yang Z and Yang Y: Novel GATA6 loss-of-function mutation responsible for familial atrial fibrillation. Int J Mol Med 30: 783-790, 2012.
APA
Li, J., Liu, W., Yang, Z., & Yang, Y. (2012). Novel GATA6 loss-of-function mutation responsible for familial atrial fibrillation. International Journal of Molecular Medicine, 30, 783-790. https://doi.org/10.3892/ijmm.2012.1068
MLA
Li, J., Liu, W., Yang, Z., Yang, Y."Novel GATA6 loss-of-function mutation responsible for familial atrial fibrillation". International Journal of Molecular Medicine 30.4 (2012): 783-790.
Chicago
Li, J., Liu, W., Yang, Z., Yang, Y."Novel GATA6 loss-of-function mutation responsible for familial atrial fibrillation". International Journal of Molecular Medicine 30, no. 4 (2012): 783-790. https://doi.org/10.3892/ijmm.2012.1068
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