A Gain-of-function Mutation in the HIF2A Gene in Familial Erythrocytosis

Overview

Journal N Engl J Med

Specialty General Medicine

Date 2008 Jan 11

PMID 18184961

Citations 152

Authors

Melanie J Percy

Paul W Furlow

Guy S Lucas

Xiping Li

Terence R J Lappin

Mary Frances McMullin

Frank S Lee

Affiliations

Soon will be listed here.

Abstract

Hypoxia-inducible factor (HIF) alpha, which has three isoforms, is central to the continuous balancing of the supply and demand of oxygen throughout the body. HIF-alpha is a transcription factor that modulates a wide range of processes, including erythropoiesis, angiogenesis, and cellular metabolism. We describe a family with erythrocytosis and a mutation in the HIF2A gene, which encodes the HIF-2alpha protein. Our functional studies indicate that this mutation leads to stabilization of the HIF-2alpha protein and suggest that wild-type HIF-2alpha regulates erythropoietin production in adults.

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