Abstract
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 language | English |
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Pages (from-to) | 5400-5402 |
Number of pages | 3 |
Journal | Blood |
Volume | 111 |
Issue number | 11 |
DOIs | |
Publication status | Published - 01 Jun 2008 |
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Immunology
- Hematology
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Identifying Patients with Rare Forms of Erythrocytosis
Mary Frances McMullin (Participant), Terence Lappin (Participant) & Anne Hughes (Participant)
Impact: Health Impact, Quality of Life Impact