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Blood, 1 June 2008, Vol. 111, No. 11, pp. 5400-5402. Prepublished online as a Blood First Edition Paper on March 31, 2008; DOI 10.1182/blood-2008-02-137703. This Article Full Text (PDF) All Versions of this Article: blood-2008-02-137703v1 111/11/5400    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Percy, M. J Articles by Lee, F. S Search for Related Content PubMed PubMed Citation Articles by Percy, M. J Articles by Lee, F. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 5, 2008 Accepted March 19, 2008 Novel Exon 12 mutations in the HIF2A gene associated with erythrocytosis Melanie J Percy*, Philip A Beer, Gavin Campbell, Ad W Dekker, Anthony R Green, David Oscier, Glenn Rainey, Richard van Wijk, Marion Wood, Terence RJ Lappin, Mary Frances McMullin, and Frank S Lee Department of Haematology, Belfast City Hospital, Belfast, Northern Ireland, United Kingdom Department of Haematology, University of Cambridge, Cambridge, United Kingdom Essex Rivers Healthcare NHS Trust, Colchester General Hospital, Colchester, Essex, United Kingdom Department of Clinical Hematology, University Medical Center Utrecht, Utrecht, Netherlands Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom Department of Haematology, Vale of Leven District General Hospital, Alexandria, Dunbartonshire, United Kingdom Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, Netherlands Centre for Cancer Research and Cell Biology, Queen's University, Belfast, Northern Ireland, United Kingdom Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, United States * Corresponding author; email: melanie.percy{at}belfasttrust.hscni.net. Erythrocytosis can arise from deregulation of the erythropoietin (Epo) axis due to defects in the oxygen-sensing pathway. Epo synthesis is controlled by the Hypoxia Inducible Factor (HIF) complex, composed of an and a subunit. There are two main a subunits, HIF-1 and HIF-2. Recently, a HIF-2 Gly537Trp mutation was identified in a family with erythrocytosis. This raises the possibility of HIF2A mutations being associated with other cases of erythrocytosis. We now report a subsequent analysis of HIF2A in a cohort of 75 erythrocytosis patients, and identify four additional patients with novel heterozygous Met535Val and Gly537Arg mutations. All individuals presented at a young age with elevated serum Epo. Mutations at Gly-537 account for four of five HIF2A mutations associated with erythrocytosis. These findings support the importance of HIF-2 in human Epo regulation and warrant investigation of HIF2A in patients with unexplained erythrocytosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. L. Semenza Involvement of oxygen-sensing pathways in physiologic and pathologic erythropoiesis Blood, September 3, 2009; 114(10): 2015 - 2019. [Abstract] [Full Text] [PDF] P. W. Furlow, M. J. Percy, S. Sutherland, C. Bierl, M. F. McMullin, S. R. Master, T. R. J. Lappin, and F. S. Lee Erythrocytosis-associated HIF-2{alpha} Mutations Demonstrate a Critical Role for Residues C-terminal to the Hydroxylacceptor Proline J. Biol. Chem., April 3, 2009; 284(14): 9050 - 9058. [Abstract] [Full Text] [PDF] M. J. Percy and F. S. Lee Familial erythrocytosis: molecular links to red blood cell control Haematologica, July 1, 2008; 93(7): 963 - 967. [Full Text] [PDF]

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