title: Familial erythrocytosis arising from a gain-of-function mutation in the HIF2A gene of the oxygen sensing pathway.
abstract: A mutation of HIF-2 alpha has been detected in three generations of a family with erythrocytosis and the mutation co-segregated with the erythrocytosis phenotype. Functional studies revealed that Gly537Trp mutation would significantly impair the function of HIF-2 alpha thus leading to increased synthesis of Epo. In addition to VHL and PHD2 a further member of the oxygen sensing pathway, namely HIF-2 alpha,can be a cause of erythrocytosis. Furthermore, HIF-2 alpha plays an important role in the regulation of Epo production. Continued study of idiopathic cases of erythrocytosis with raised serum Epo will reveal whether HIF-2 alpha will be a major cause of erythrocytosis on par with VHL.
authors: Department of Haematology, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK. melanie.percy@belfastrust.hscni.net
authors: Melanie J
authors: MJ
authors: Percy
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000097:blood / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004912:Erythrocytes / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D010100:Oxygen / Q000378:metabolism*; D010375:Pedigree; D011086:Polycythemia / Q000097:blood / Q000235:genetics*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D010100:Oxygen; D000099162:Endothelial PAS Domain-Containing Protein 1