Prevalence and spectrum of NKX2.5 mutations in patients with congenital atrial septal defect and atrioventricular block

  • Authors:
    • Ying‑Jia Xu
    • Xing‑Biao Qiu
    • Fang Yuan
    • Hong‑Yu Shi
    • Lei Xu
    • Xu‑Min Hou
    • Xin‑Kai Qu
    • Xu Liu
    • Ri‑Tai Huang
    • Song Xue
    • Yi‑Qing Yang
    • Ruo‑Gu Li
  • View Affiliations

  • Published online on: February 24, 2017     https://doi.org/10.3892/mmr.2017.6249
  • Pages: 2247-2254
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Abstract

Congenital atrial septal defect (ASD) and progressive atriventricular block (AVB) are the two most common phenotypes linked to NK2 homeobox 5 (NKX2.5) mutations in animals and humans. However, the prevalence and spectrum of NKX2.5 mutation in patients with ASD and AVB remain to be elucidated. In the present study, the coding exons and flanking introns of the NKX2.5 gene, which encodes a homeobox‑containing transcription factor essential for development of the heart, were sequenced in a cohort of 62 unrelated patients with ASD and AVB, and subsequently in a mutation carrier's available family members. As controls, 300 unrelated, ethnically‑matched healthy individuals were recruited, who were also genotyped for NKX2.5. The functional consequence of the mutant NKX2.5 was evaluated in contrast to its wild‑type counterpart using a dual‑luciferase reporter assay system. As a result, a novel heterozygous NKX2.5 mutation, p.Q181X, was identified in an index patient with ASD and AVB, with a prevalence of ~1.61%. Genetic analysis of the proband's pedigree revealed that the mutation co‑segregated with ASD and AVB with complete penetrance. The nonsense mutation, which eliminated partial homeobox and the carboxyl terminus, was absent in the 600 control chromosomes. Functional evaluation showed that the NKX2.5 mutant had no transcriptional activity. Furthermore, the mutation disrupted the synergistic activation between NKX2.5 and GATA binding protein 4, another cardiac core transcription factor associated with ASD. The results of the present study expand the spectrum of NKX2.5 mutations linked to ASD and AVB, and indicated that NKX2.5 loss‑of‑function mutations are an uncommon cause of ASD and AVB in humans.
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April-2017
Volume 15 Issue 4

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

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Spandidos Publications style
Xu YJ, Qiu XB, Yuan F, Shi HY, Xu L, Hou XM, Qu XK, Liu X, Huang RT, Xue S, Xue S, et al: Prevalence and spectrum of NKX2.5 mutations in patients with congenital atrial septal defect and atrioventricular block. Mol Med Rep 15: 2247-2254, 2017
APA
Xu, Y., Qiu, X., Yuan, F., Shi, H., Xu, L., Hou, X. ... Li, R. (2017). Prevalence and spectrum of NKX2.5 mutations in patients with congenital atrial septal defect and atrioventricular block. Molecular Medicine Reports, 15, 2247-2254. https://doi.org/10.3892/mmr.2017.6249
MLA
Xu, Y., Qiu, X., Yuan, F., Shi, H., Xu, L., Hou, X., Qu, X., Liu, X., Huang, R., Xue, S., Yang, Y., Li, R."Prevalence and spectrum of NKX2.5 mutations in patients with congenital atrial septal defect and atrioventricular block". Molecular Medicine Reports 15.4 (2017): 2247-2254.
Chicago
Xu, Y., Qiu, X., Yuan, F., Shi, H., Xu, L., Hou, X., Qu, X., Liu, X., Huang, R., Xue, S., Yang, Y., Li, R."Prevalence and spectrum of NKX2.5 mutations in patients with congenital atrial septal defect and atrioventricular block". Molecular Medicine Reports 15, no. 4 (2017): 2247-2254. https://doi.org/10.3892/mmr.2017.6249