Autosomal dominant erythrocytosis and pulmonary arterial hypertension associated with an activating HIF2 alpha mutation.

@article{Gale2008AutosomalDE,
  title={Autosomal dominant erythrocytosis and pulmonary arterial hypertension associated with an activating HIF2 alpha mutation.},
  author={Daniel P. Gale and Sarah K. Harten and C Reid and Edward G. D. Tuddenham and Patrick H. Maxwell},
  journal={Blood},
  year={2008},
  volume={112 3},
  pages={
          919-21
        }
}
To the editor: Erythropoietin production is regulated by the transcription factor hypoxia-inducible factor (HIF). Erythrocytosis with raised erythropoietin levels due to dysregulated HIF activity is recognized as a consequence of a hypomorphic HIFα E3 ubiquitin ligase ( VHL ) allele (Chuvash 

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Dysregulation of the HIF pathway due to VHL mutation causing severe erythrocytosis and pulmonary arterial hypertension.
TLDR
There is increasing evidence thatreditary erythrocytosis can be caused by mutations in genes involved in the hypoxia-inducible factor (HIF) pathway.
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  • G. Semenza
  • Medicine, Biology
    American journal of medical genetics. Part A
  • 2021
TLDR
Mutations that dysregulate HIF activity are the genetic basis for tumor predisposition in the von Hippel–Lindau syndrome and excess red blood cell production in hereditary erythrocytosis.
Heritable disorders of oxygen sensing
  • G. Semenza
  • Medicine, Biology
    American journal of medical genetics. Part A
  • 2021
TLDR
Mutations that dysregulate HIF activity are the genetic basis for tumor predisposition in the von Hippel–Lindau syndrome and excess red blood cell production in hereditary erythrocytosis.
Erythrocytosis and Pulmonary Hypertension in a Mouse Model of Human HIF2A Gain of Function Mutation*
TLDR
These findings firmly establish missense mutations in HIF-2α as a cause of erythrocytosis, highlight the importance of this Hif-α isoform in erythropoiesis, and point to physiologic consequences of HIF -2α dysregulation.
Cardiopulmonary phenotype associated with human PHD2 mutation
Oxygen‐dependent regulation of the erythropoietin gene is mediated by the hypoxia‐inducible factor (HIF) family of transcription factors. When oxygen is plentiful, HIF undergoes hydroxylation by a
Congenital erythrocytosis associated with gain-of-function HIF2A gene mutations and erythropoietin levels in the normal range
TLDR
The identification of two cases of familial erythrocytosis associated with heterozygous HIF2A missense mutations, namely Ile533Val and Gly537Arg, suggest the novel proposal that polycythemia observed in subjects with Hif2A mutations might also be due to primary changes in hematopoietic cells and not only secondary to increased erythropoietin levels.
Erythrocytosis associated with a novel missense mutation in the HIF2A gene
TLDR
A new erythrocytosis-associated mutation is reported, p.Asp539Glu, in the HIF2A gene that compromises binding of HIF-2α to both PHD2 and VHL, and it is proposed that this mutation is the cause of ery throat cancer in this individual.
Genetic variability of hypoxia‐inducible factor alpha (HIFA) genes in familial erythrocytosis: Analysis of the literature and genome databases
TLDR
Sixteen out of 20 variants in the EPAS1 gene are positioned in a conserved region of 13 amino acids within exon 12, next to regulatory post‐translational modification and binding sites, suggesting that EPAS 1 has an important role in erythropoiesis.
HIF pathway mutations and erythrocytosis
  • M. McMullin
  • Biology, Medicine
    Expert review of hematology
  • 2010
TLDR
A number of mutations in the VHL, PHD2, and HIF2A genes have been identified in individuals and these mutations lead to erythrocytosis, which may include some major thromboembolic events in young patients.
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