title: Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis.
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 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.
authors: Department of Haematology, Belfast City Hospital, Belfast, United Kingdom. melanie.percy@belfasttrust.hscni.net
authors: Melanie J
authors: MJ
authors: Percy
authors: Philip A
authors: PA
authors: Beer
authors: Gavin
authors: G
authors: Campbell
authors: Ad W
authors: AW
authors: Dekker
authors: Anthony R
authors: AR
authors: Green
authors: David
authors: D
authors: Oscier
authors: M Glenn
authors: MG
authors: Rainey
authors: Richard
authors: R
authors: van Wijk
authors: Marion
authors: M
authors: Wood
authors: Terence R J
authors: TR
authors: Lappin
authors: Mary Frances
authors: MF
authors: McMullin
authors: Frank S
authors: FS
authors: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004921:Erythropoietin / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011086:Polycythemia / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004921:Erythropoietin; D000099162:Endothelial PAS Domain-Containing Protein 1