The homozygous VHL(D126N) missense mutation is associated with dramatically elevated erythropoietin levels, consequent polycythemia, and early onset severe pulmonary hypertension

Pediatr Blood Cancer. 2014 Nov;61(11):2104-6. doi: 10.1002/pbc.25056. Epub 2014 Apr 12.

Abstract

von Hippel-Lindau (VHL) protein is the principal negative regulator of hypoxia sensing mediated by transcription factors. Mutations in exon 3 of the VHL gene lead to Chuvash (VHL(R200W)) and Croatian (VHL(H191D)) polycythemias. Here, we describe an infant of Bangladesh ethnicity with a novel homozygous VHL(D126N) mutation with congenital polycythemia and dramatically elevated erythropoietin (EPO) levels, who developed severe fatal pulmonary hypertension. In contrast to Chuvash polycythemia, erythroid progenitors (BFU-Es) did not reveal a marked EPO hypersensitivity. Further, NF-E2 and RUNX1 transcripts that correlate with BFU-Es EPO hypersensitivity in polycythemic mutations were not elevated.

Keywords: erythropoietin; polycythemia; pulmonary hypertension; von Hippel-Lindau gene.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Erythropoietin / blood*
  • Humans
  • Hypertension, Pulmonary / genetics*
  • Infant
  • Male
  • Mutation, Missense*
  • Polycythemia / genetics*
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics*

Substances

  • EPO protein, human
  • Erythropoietin
  • Von Hippel-Lindau Tumor Suppressor Protein
  • VHL protein, human