| Title | Novel Exon 12 mutations in the HIF2A gene associated with erythrocytosis. | | Author(s) | 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 | | Institution | Department of Haematology, Belfast City Hospital, Belfast, Northern Ireland, United Kingdom. | | Source | Blood 2008 Mar 31. | | Abstract | 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18378852 |
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