1. EGLN1 mutations in Cis can induce congenital erythrocytosis with thromboses by increasing protein instability.
- Author
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Carillo S, Delamare M, Henry L, Maaziz N, Safraou H, Gardie B, and Lavabre-Bertrand T
- Subjects
- Humans, Female, Male, Pedigree, Mutation, Adult, Mutation, Missense, Polycythemia genetics, Polycythemia congenital, Hypoxia-Inducible Factor-Proline Dioxygenases genetics, Protein Stability
- Abstract
Hereditary congenital erythrocytosis results from constitutive activation of the hypoxia pathway. This pathway is controlled by regulation of the α isoforms of the hypoxia-inducible factor α/β heterodimer, notably via hydroxylation by prolyl hydroxylase domain 2 (PHD2). Mutations affecting PHD2 are involved in Type 3 erythrocytosis. We report an atypical family bearing two PHD2 mutations located in Cis (L195H and E225D) transmitted in a dominant feature, together with a phenotypic analysis, structural modelling and functional study. Mutations have a cumulative effect, with E255D playing the major role, and severely compromised PHD2 stability, probably explaining why the hypoxia pathway at the origin of the disease is activated., (© 2025 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2025
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