Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis.

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    • M.J. Percy
    • P.A. Beer
    • G. Campbell
    • A.W. Dekker
    • A.R. Green
    • D. Oscier
    • M.G. Rainey
    • R. Van Wijk
    • M. Wood
    • Terence Lappin
    • Mary McMullin
    • F.S. Lee

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    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 a and a ß subunit. There are 2 main a subunits, HIF-1a and HIF-2a. Recently, a HIF-2a 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-2a in human Epo regulation and warrant investigation of HIF2A in patients with unexplained erythrocytosis.
    Original languageEnglish
    Number of pages3
    Pages (from-to)5400-5402
    JournalBlood
    Journal publication date01 Jun 2008
    Issue number11
    Volume111
    DOIs
    Publication statusPublished - 01 Jun 2008

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