A novel NKX2-5 mutation in familial ventricular septal defect

  • Authors:
    • Juan Wang
    • Yuan-Feng Xin
    • Xing-Yuan Liu
    • Zhong-Min Liu
    • Xiao-Zhong Wang
    • Yi-Qing Yang
  • View Affiliations

  • Published online on: Thursday, December 16, 2010
  • Pages: 369-375
  • DOI: 10.3892/ijmm.2010.585

Abstract

Ventricular septal defect (VSD) is the most common cardiovascular malformation and an important contributor to the substantial morbidity and mortality in infancy. Growing evidence suggests that genetic defects play important roles in the pathogenesis of congenital VSD. However, VSD is of great genetic heterogeneity and the genetic basis for VSD in the majority of the patients remains largely unhnown. In this study, the entire coding region of the NKX2-5 gene, which encodes a homeodomain-containing transcription factor crucial to cardiogenesis, was initially sequenced in 136 unrelated patients with VSD. The relatives of a proband harboring the identified mutation and 200 unrelated control individuals were genotyped. The functional characteristic of the mutant transcription factor was analyzed in contrast to its wild-type counterpart using a luciferase reporter assay system. A novel heterozygous NKX2-5 mutation, p.P59A, was identified in a family with autosomal dominant inherited VSD. Absent in the 200 control individuals, the mutation was highly conserved evolutionarily and co-segregated with VSD in the family with complete penetrance. Functional analysis revealed that the p.P59A mutation of NKX2-5 was associated with a decreased transcriptional activity. These findings expand the spectrum of the mutations in NKX2-5 linked to VSD and provide new insight into the molecular mechanisms involved in VSD. The resuls of the present study may have potential implications in the genetic diagnosis and gene-specific therapy of this common childhood disease.
Journal Cover

March 2011
Volume 27 Issue 3

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

2013 Impact Factor: 1.88
Ranked #27/122 Medicine Research and Experimental
(total number of cites)

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APA
Wang, J., Xin, Y., Liu, X., Liu, Z., Wang, X., & Yang, Y. (2011). A novel NKX2-5 mutation in familial ventricular septal defect. International Journal of Molecular Medicine, 27(3), 369-375.
MLA
Wang, Xin, Liu, Liu, Wang, and Yi-Qing Yang. "A novel NKX2-5 mutation in familial ventricular septal defect." International Journal of Molecular Medicine International Journal of Molecular Medicine 27.3 (2011): 369-375.
Chicago
Wang, Xin, Liu, Liu, Wang, and Yi-Qing Yang. "A novel NKX2-5 mutation in familial ventricular septal defect." International Journal of Molecular Medicine International Journal of Molecular Medicine 27 no. 3 (2011): 369-375.