A study of 36 unrelated cases with pure erythrocytosis revealed three new mutations in the erythropoietin receptor gene

Haematologica. 2008 Jul;93(7):1072-5. doi: 10.3324/haematol.12260. Epub 2008 May 19.

Abstract

Thirty-six unrelated cases with erythrocytosis of unknown origin were investigated. Exons 5-8 of the erythropoietin receptor gene (EPOR), the von Hippel-Lindau gene, and the prolyl hydroxylase domain protein 2 gene (PHD2) were screened by direct DNA sequencing. The Janus kinase 2 mutation, JAK2 (Val617Phe), was screened by allele specific PCR. In this study, three new mutations of EPOR causing deletions in exon 8 were found: the first led directly to a stop codon [g.5957_5958delTT (p.Phe424X)], the second to a stop codon after one residue [g.5828_5829delCC (p.Pro381GlnfsX1)] and the third to a stop codon following a frameshift sequence of 23 residues [g.5971delC (p.Leu429TrpfsX23)]. One patient had a previously reported EPOR mutation [g.6146A>G (p.Asn487Ser)] and another, a silent one (g.5799G>A). All were heterozygotes. In addition, 2 patients were positive for JAK2 (Val617Phe), and 2 reported elsewhere, were mutated in the PHD2 gene [c.606delG (p.Met202IlefsX71).

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Female
  • Gene Expression Regulation*
  • Humans
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Male
  • Middle Aged
  • Mutation*
  • Polycythemia / diagnosis*
  • Polycythemia / genetics*
  • Procollagen-Proline Dioxygenase / genetics
  • Receptors, Erythropoietin / genetics*
  • Receptors, Erythropoietin / metabolism
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism

Substances

  • Receptors, Erythropoietin
  • EGLN1 protein, human
  • Procollagen-Proline Dioxygenase
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Von Hippel-Lindau Tumor Suppressor Protein