Two new mutations in the HIF2A gene associated with erythrocytosis |
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| Authors: | Percy Melanie J Chung Yu Jin Harrison Claire Mercieca Jane Hoffbrand A Victor Dinardo Carla L Santos Paulo C J L Fonseca Guilherme H H Gualandro Sandra F M Pereira Alexandre C Lappin Terence R J McMullin Mary Frances Lee Frank S |
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| Affiliation: | 1. Department of Haematology, Belfast City Hospital, Belfast, Northern Ireland BT9 7AB, United Kingdom;2. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;3. Department of Haematology, St. Thomas' Hospital, London SE1 7EH, United Kingdom;4. St. Helier Hospital, Carshalton, SM5 1AA United Kingdom;5. Department of Haematology, Royal Free Hospital, London NW3 2QG, United Kingdom;6. Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Sao Paulo, Brazil;7. Department of Hematology, University of Sao Paulo Medical School, Sao Paulo, Brazil;8. Centre for Cancer Research and Cell Biology, Queen's University, Belfast, Northern Ireland BT9 7AB, United Kingdom |
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| Abstract: | Congenital or familial erythrocytosis/polycythemia can have many causes, and an emerging cause is genetic disruption of the oxygen‐sensing pathway that regulates the Erythropoietin (EPO) gene. More specifically, recent studies have identified erythrocytosis‐associated mutations in the HIF2A gene, which encodes for Hypoxia Inducible Factor‐2α (HIF‐2α), as well as in two genes that encode for proteins that regulate it, Prolyl Hydroxylase Domain protein 2 (PHD2) and the von Hippel Lindau tumor suppressor protein (VHL). We report here the identification of two new heterozygous HIF2A missense mutations, M535T, and F540L, both associated with erythrocytosis. Met‐535 has previously been identified as a residue mutated in other patients with erythrocytosis; although, the mutation of this particular residue to Thr has not been reported. In contrast, Phe‐540 has not been reported as a residue mutated in erythrocytosis, and we present evidence here that this mutation impairs interaction of HIF‐2α with both VHL and PHD2. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc. |
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