Isolated Erythrocytosis Associated With 3 Novel Missense Mutations in the EGLN1 Gene. (July 2020)

• Record Type: Journal Article
• Authors: Moore, Joseph A.; Hubbi, Maimon E.; Wang, Chenliang; Wang, Yingfei; Luo, Weibo; Hofmann, Sandra; Rambally, Siayareh
• Is Part Of: Journal of investigative medicine high impact case reports. Volume 8(2020)
• Publication Date: 2020-07
• Subjects: erythrocytosis -- EGLN1 -- PHD2 -- HIF-1 -- polycythemia; Internal medicine -- Periodicals; Medical care -- Periodicals; 616.005
• DOI: 10.1177/2324709620947256
• Languages: English
• ISSNs: 2324-7096

Abstract

Hypoxia-inducible factor-1 (HIF-1) is a key regulator of erythropoiesis. In this article, we report 3 novel mutations, P378S, A385T, and G206C, on the EGLN1 gene encoding the negative HIF-1α regulator prolyl hydroxylase domain-2 (PHD2) in 3 patients with isolated erythrocytosis. These mutations impair PHD2 protein stability and partially reduce PHD2 activity, leading to increased HIF-1α protein levels in cultured cells.