Percy MJ, Beer PA, Campbell G, Dekker AW, Green AR, Oscier D, Rainey G, van Wijk R, Wood M, Lappin TR, McMullin MF, Lee FS
Novel Exon 12 mutations in the HIF2A gene associated with erythrocytosis. [JOURNAL ARTICLE]
Blood 2008 Mar 31.
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 alpha and a beta subunit. There are two main a alpha subunits, HIF-1alpha and HIF-2alpha. Recently, a HIF-2alpha 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-2alpha in human Epo regulation and warrant investigation of HIF2A in patients with unexplained erythrocytosis.
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