Isolated Erythrocytosis Associated With 3 Novel Missense Mutations in the EGLN1 Gene
Open Access
- 1 January 2020
- journal article
- case report
- Published by SAGE Publications in Journal of Investigative Medicine High Impact Case Reports
- Vol. 8
Abstract
Hypoxia-inducible factor-1 (HIF-1) is a key regulator of erythropoiesis. In this article, we report 3 novel mutations, P378S, A385T, and G206C, on the EGLN1 gene encoding the negative HIF-1α regulator prolyl hydroxylase domain-2 (PHD2) in 3 patients with isolated erythrocytosis. These mutations impair PHD2 protein stability and partially reduce PHD2 activity, leading to increased HIF-1α protein levels in cultured cells.Keywords
Funding Information
- Cancer Prevention and Research Institute of Texas (RR140036)
- National Institutes of Health (R00CA168746)
- National Institutes of Health (R00NS078049)
- National Institutes of Health (R35GM124693)
This publication has 14 references indexed in Scilit:
- Regulation of cell proliferation by hypoxia-inducible factorsAmerican Journal of Physiology-Cell Physiology, 2015
- Hypoxia-Inducible Factors in Physiology and MedicineCell, 2012
- Isolated erythrocytosis: study of 67 patients and identification of three novel germ-line mutations in the prolyl hydroxylase domain protein 2 (PHD2) geneHaematologica, 2011
- Oxygen Sensing by Metazoans: The Central Role of the HIF Hydroxylase PathwayMolecular Cell, 2008
- HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylationProceedings of the National Academy of Sciences, 2001
- HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 SensingScience, 2001
- Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl HydroxylationScience, 2001
- Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1αGenes & Development, 1998
- Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.Proceedings of the National Academy of Sciences, 1995
- A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation.Molecular and Cellular Biology, 1992