Isolated Erythrocytosis Associated With 3 Novel Missense Mutations in the EGLN1 Gene

J Investig Med High Impact Case Rep. 2020 Jan-Dec:8:2324709620947256. doi: 10.1177/2324709620947256.

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: EGLN1; HIF-1; PHD2; erythrocytosis; polycythemia.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Humans
  • Hypoxia-Inducible Factor-Proline Dioxygenases / genetics*
  • Male
  • Middle Aged
  • Mutation, Missense
  • Polycythemia / genetics*
  • Procollagen-Proline Dioxygenase / genetics

Substances

  • EGLN1 protein, human
  • Procollagen-Proline Dioxygenase
  • Hypoxia-Inducible Factor-Proline Dioxygenases