NRP1 haploinsufficiency predisposes to the development of Tetralogy of Fallot

Ivan Duran, Jessica Tenney, Carmen M. Warren, Anna Sarukhanov, Fabiana Csukasi, Mark Skalansky, Maria L. Iruela-Arispe, Deborah Krakow*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. It involves anatomical abnormalities that change the normal flow of blood through the heart resulting in low oxygenation. Although not all of the underlying causes of TOF are completely understood, the disease has been associated with varying genetic etiologies including chromosomal abnormalities and Mendelian disorders, but can also occur as an isolated defect. In this report, we describe a familial case of TOF associated with a 1.8 Mb deletion of chromosome 10p11. Among the three genes in the region one is Neuropilin1 (NRP1), a membrane co-receptor of VEGF that modulates vasculogenesis. Hemizygous levels of NRP1 resulted in a reduced expression at the transcriptional and protein levels in patient-derived cells. Reduction of NRP1 also lead to decreased function of its activity as a co-receptor in intermolecular VEGF signaling. These findings support that diminished levels of NRP1 contribute to the development of TOF, likely through its function in mediating VEGF signal and vasculogenesis.

Original languageEnglish (US)
Pages (from-to)649-656
Number of pages8
JournalAmerican Journal of Medical Genetics, Part A
Volume176
Issue number3
DOIs
StatePublished - Mar 2018

Keywords

  • chromosomal deletion
  • congenital heart disease
  • neuropilin 1 (NRP1)
  • prenatal ultrasound
  • tetralogy of fallot (TOF)

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Duran, I., Tenney, J., Warren, C. M., Sarukhanov, A., Csukasi, F., Skalansky, M., Iruela-Arispe, M. L., & Krakow, D. (2018). NRP1 haploinsufficiency predisposes to the development of Tetralogy of Fallot. American Journal of Medical Genetics, Part A, 176(3), 649-656. https://doi.org/10.1002/ajmg.a.38600