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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 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 Citation Map 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. Related Collections Red Cells Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Brief Report Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis Melanie J. Percy1, Philip A. Beer2, Gavin Campbell3, Ad W. Dekker4, Anthony R. Green2, David Oscier5, M. Glenn Rainey6, Richard van Wijk7, Marion Wood3, Terence R. J. Lappin8, Mary Frances McMullin1,8, and Frank S. Lee9 1 Department of Haematology, Belfast City Hospital, Belfast, United Kingdom; 2 Department of Haematology, University of Cambridge, Cambridge, United Kingdom; 3 Essex Rivers Healthcare National Health Service (NHS) Trust, Colchester General Hospital, Colchester, United Kingdom; 4 Department of Clinical Hematology, University Medical Center Utrecht, Utrecht, The Netherlands; 5 Department of Haematology, Royal Bournemouth Hospital, Bournemouth, United Kingdom; 6 Department of Haematology, Vale of Leven District General Hospital, Alexandria, United Kingdom; 7 Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, The Netherlands; 8 Centre for Cancer Research and Cell Biology, Queen's University, Belfast, United Kingdom; and 9 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia Erythrocytosis can arise from deregulation of the erythropoietin (Epo) axis resulting from defects in the oxygen-sensing pathway. Epo synthesis is controlled by the hypoxia inducible factor (HIF) complex, composed of an and a β subunit. There are 2 main 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 4 additional patients with novel heterozygous Met535Val and Gly537Arg mutations. All patients presented at a young age with elevated serum Epo. Mutations at Gly-537 account for 4 of 5 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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