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A novel KLF13 mutation underlying congenital patent ductus arteriosus and ventricular septal defect, as well as bicuspid aortic valve

  • Authors:
    • Pradhan Abhinav
    • Gao-Feng Zhang
    • Cui-Mei Zhao
    • Ying-Jia Xu
    • Juan Wang
    • Yi-Qing Yang

  • View Affiliations

  • Published online on: March 1, 2022     https://doi.org/10.3892/etm.2022.11240
  • Article Number: 311

  • Copyright: © Abhinav et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Recently, mutations in the Kruppel‑like factor 13 (KLF13) gene encoding a Kruppel‑like transcription factor have been reported to cause congenital heart disease (CHD). However, due to pronounced genetic heterogeneity, the mutational spectrum of KLF13 in other cohorts of cases suffering from distinct types of CHD remain to be ascertained. In the present investigation, by Sanger sequencing of KLF13 in 316 unrelated cases affected by different forms of CHD, a new mutation in heterozygous status, NM_015995.3: c.430G>T; p.(Glu144*), was detected in an index patient affected with patent ductus arteriosus (PDA) and ventricular septal defect (VSD), as well as bicuspid aortic valve (BAV), with a mutation frequency of ~0.32%. Genetic investigation of the available family members of the proband demonstrated that the truncating mutation co‑segregated with CHD. The nonsense mutation was not observed in 400 unrelated volunteers without CHD who were enrolled as control subjects. Quantitative biological measurements with dual luciferase reporters revealed that Glu144*‑mutant KLF13 did not transactivate the downstream genes vascular endothelial growth factor A and natriuretic peptide A. In addition, the mutation abrogated the synergistic transcriptional activation between KLF13 and T‑box transcription factor 5, a well‑established CHD‑causing gene. In conclusion, the present study indicates that genetically defective KLF13 contributes to familial PDA and VSD, as well as BAV, which expands the phenotypic spectrum linked to KLF13, and reveals a novel molecular pathogenesis of the disease, providing a new molecular target for the early prophylaxis and individualized treatment of CHD.
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April-2022
Volume 23 Issue 4

Print ISSN: 1792-0981
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Spandidos Publications style
Abhinav P, Zhang G, Zhao C, Xu Y, Wang J and Yang Y: A novel <em>KLF13</em> mutation underlying congenital patent ductus arteriosus and ventricular septal defect, as well as bicuspid aortic valve. Exp Ther Med 23: 311, 2022.
APA
Abhinav, P., Zhang, G., Zhao, C., Xu, Y., Wang, J., & Yang, Y. (2022). A novel <em>KLF13</em> mutation underlying congenital patent ductus arteriosus and ventricular septal defect, as well as bicuspid aortic valve. Experimental and Therapeutic Medicine, 23, 311. https://doi.org/10.3892/etm.2022.11240
MLA
Abhinav, P., Zhang, G., Zhao, C., Xu, Y., Wang, J., Yang, Y."A novel <em>KLF13</em> mutation underlying congenital patent ductus arteriosus and ventricular septal defect, as well as bicuspid aortic valve". Experimental and Therapeutic Medicine 23.4 (2022): 311.
Chicago
Abhinav, P., Zhang, G., Zhao, C., Xu, Y., Wang, J., Yang, Y."A novel <em>KLF13</em> mutation underlying congenital patent ductus arteriosus and ventricular septal defect, as well as bicuspid aortic valve". Experimental and Therapeutic Medicine 23, no. 4 (2022): 311. https://doi.org/10.3892/etm.2022.11240