• Melanie J Percy, Philip A Beer, Gavin Campbell, Ad W Dekker, Anthony R Green, David Oscier, M Glenn Rainey, Richard van Wijk, Marion Wood, Terence R J Lappin, Mary Frances McMullin, and Frank S Lee.
• Department of Haematology, Belfast City Hospital, Belfast, United Kingdom. melanie.percy@belfasttrust.hscni.net
• Blood. 2008 Jun 1; 111 (11): 5400-2.

AbstractErythrocytosis 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 alpha and a beta subunit. There are 2 main alpha subunits, HIF-1 alpha and HIF-2 alpha. Recently, a HIF-2 alpha 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 alpha in human Epo regulation and warrant investigation of HIF2A in patients with unexplained erythrocytosis.

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