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

• Published in: Haematologica (Roma) 2008-07, Vol.93 (7), p.1072-1075
• Main Authors: Al-Sheikh, Maha, Mazurier, Elodie, Gardie, Betty, Casadevall, Nicole, Galacteros, Frederic, Goossens, Michel, Wajcman, Henri, Prehu, Claude, Ugo, Valerie
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Child; Diseases of red blood cells; Female; Gene Expression Regulation; Hematologic and hematopoietic diseases; Humans; Hypoxia-Inducible Factor-Proline Dioxygenases; Male; Medical sciences; Middle Aged; Mutation; Polycythemia - diagnosis; Polycythemia - genetics; Polycythemias; Procollagen-Proline Dioxygenase - genetics; Receptors, Erythropoietin - genetics; Receptors, Erythropoietin - metabolism; Von Hippel-Lindau Tumor Suppressor Protein - metabolism
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.12260

1 INSERM, U841, Créteil 2 Service de Biochimie et Génétique, AP-HP, Groupe Henri Mondor, Albert Chenevier, Créteil 3 Unité de Génétique du Globules Rouges, AP-HP, Groupe Henri Mondor, Albert Chenevier 4 Service Hématologie Biologique, AP-HP, Hôpital Hôtel Dieu, Paris 5 Institut Gustave Roussy, Villejuif 6 Laboratoire d’hématologie, Centre Hospitalier Universitaire de Brest, Université de Bretagne Occidentale, Brest, France Correspondence: Valérie Ugo, Laboratoire d’Hématologie, Hôpital Morvan, Centre Hospitalier Universitaire de Brest, 5 Avenue Foch, 29200 Brest, France. E-mail: valerie.ugo{at}chu-brest.fr 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). Key words: polycythemia, erythrocytosis, erythropoietin receptor, von Hippel-Lindau, JAK2, prolyl hydroxylase domain protein 2. Related Article Familial erythrocytosis: molecular links to red blood cell control Melanie J. Percy, Frank S. Lee Haematologica 2008 93: 963-967. [Full Text] [PDF]