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: Melanie J Percy
• Journal: The Ulster medical journal (Ulster Med J) Vol. 77 Issue 2 Pg. 86-8 (May 2008) ISSN: 0041-6193 [Print] Northern Ireland
• PMID: 18711622 (Publication Type: Journal Article, Review)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• endothelial PAS domain-containing protein 1
• DNA
• Oxygen

Topics

• Animals
• Basic Helix-Loop-Helix Transcription Factors (blood, genetics)
• DNA (genetics)
• Erythrocytes (metabolism)
• Genetic Predisposition to Disease
• Humans
• Mutation
• Oxygen (metabolism)
• Pedigree
• Polycythemia (blood, genetics)