A novel TBX20 loss‑of‑function mutation contributes to adult‑onset dilated cardiomyopathy or congenital atrial septal defect

  • Authors:
    • Yi‑Meng Zhou
    • Xiao‑Yong Dai
    • Ri‑Tai Huang
    • Song Xue
    • Ying‑Jia Xu
    • Xing‑Biao Qiu
    • Yi‑Qing Yang
  • View Affiliations

  • Published online on: August 9, 2016     https://doi.org/10.3892/mmr.2016.5609
  • Pages: 3307-3314
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Dilated cardiomyopathy (DCM) is the most prevalent form of primary cardiomyopathy in humans and is a leading cause of heart failure and sudden cardiac death. Genetic abnormalities have been demonstrated to be a major contributor to the development of DCM. However, DCM is a genetically heterogeneous disease, and the genetic basis underlying DCM in a significant proportion of patients remains unclear. In the current study, the coding exons and splicing junction sites of the T‑Box 20 (TBX20) gene, which encodes a T‑box transcription factor essential for cardiac morphogenesis and structural remodeling, were sequenced in 115 unrelated patients with idiopathic DCM, and a novel heterozygous mutation, p.E143X, was identified in one patient. Genetic analysis of the mutation carrier's pedigree indicated that the nonsense mutation was present in all the living family members with DCM, and also in a female patient with a congenital atrial septal defect. The mutation, which was predicted to generate a truncated protein with only the N‑terminus and a fraction of the T‑box domain remaining, was absent in 800 control chromosomes. Functional assays using a dual‑luciferase reporter assay system revealed that the truncated TBX20 protein had no transcriptional activity in contrast to its wild‑type counterpart. Furthermore, the mutation abolished the synergistic activation between TBX20 and NK2 homeobox 5, or between TBX20 and GATA binding protein 4. The observations of the current study expand the mutation spectrum of TBX20 associated with DCM and congenital heart disease (CHD), which provide novel insight into the molecular mechanisms underlying DCM and CHD, suggesting the potential implications for the effective and personalized treatment of these diseases.
View Figures
View References

Related Articles

Journal Cover

October-2016
Volume 14 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhou YM, Dai XY, Huang RT, Xue S, Xu YJ, Qiu XB and Yang YQ: A novel TBX20 loss‑of‑function mutation contributes to adult‑onset dilated cardiomyopathy or congenital atrial septal defect. Mol Med Rep 14: 3307-3314, 2016
APA
Zhou, Y., Dai, X., Huang, R., Xue, S., Xu, Y., Qiu, X., & Yang, Y. (2016). A novel TBX20 loss‑of‑function mutation contributes to adult‑onset dilated cardiomyopathy or congenital atrial septal defect. Molecular Medicine Reports, 14, 3307-3314. https://doi.org/10.3892/mmr.2016.5609
MLA
Zhou, Y., Dai, X., Huang, R., Xue, S., Xu, Y., Qiu, X., Yang, Y."A novel TBX20 loss‑of‑function mutation contributes to adult‑onset dilated cardiomyopathy or congenital atrial septal defect". Molecular Medicine Reports 14.4 (2016): 3307-3314.
Chicago
Zhou, Y., Dai, X., Huang, R., Xue, S., Xu, Y., Qiu, X., Yang, Y."A novel TBX20 loss‑of‑function mutation contributes to adult‑onset dilated cardiomyopathy or congenital atrial septal defect". Molecular Medicine Reports 14, no. 4 (2016): 3307-3314. https://doi.org/10.3892/mmr.2016.5609