Isolated erythrocytosis: study of 67 patients and identification of three novel germ-line mutations in the prolyl hydroxylase domain protein 2 (PHD2) gene
Open accessAbstract
The oxygen sensing pathway modulates erythropoietin expression. In normal cells, intracellular oxygen tensions are directly sensed by prolyl hydroxylase domain (PHD)-containing proteins. PHD2 isozyme has a key role in tagging hypoxia-inducible factor (HIF)-α subunits for polyubiquitination and proteasomal degradation. Erythrocytosis-associated PHD2 mutations reduce hydroxylation of HIF-α. The investigation of 67 patients with isolated erythrocytosis, either sporadic or familial, allowed the identification of three novel mutations in the catalytic domain of the PHD2 protein. All new mutations are germ-line, heterozygous and missense, and code for a predicted full length mutant PHD2 protein. Identification of the disease-causing genes will be of critical importance for a better classification of familial and acquired erythrocytosis, offering additional insight into the erythropoietin regulating oxygen sensing pathway.
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Patients heterozygous for PHD2 mutations are characterized by increased red blood cell values with inappropriately normal serum EPO levels.
“Patients, who were heterozygous for these mutations were characterized by increased rbc values in the presence of inappropriately normal serum EPO levels. 157–162”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [162]
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- Authors
- Albiero, E., Ruggeri, M., Fortuna, S., Finotto, S., Bernardi, M., Madeo, D., & Rodeghiero, F.
- Affiliations
- Ospedale San Bortolo (IT)
- Corresponding author
- Rodeghiero, F.
- Venue
- Haematologica
- Published
- 2011-08-09
- Volume
- 97
- Issue
- 1
- Pages
- 123-127
- ISSN
- 0390-6078 (ISSN-L)
- 1592-8721
- PMC
- PMC3248940
- OpenAlex
- W2121922584
- Cited by
- 28
- References
- 24
- Citations by year
- 2024: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 1 · 2014: 5 · 2013: 6 · 2012: 3
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Haematologica (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Genetics › Myeloproliferative Neoplasms: Diagnosis and Treatment
- Keywords
- germline mutations, missense mutations, hypoxia-inducible factor alpha, erythropoietin regulation, familial erythrocytosis, polyubiquitination
- MeSH terms
- Adult, Base Sequence, Heterozygote, Humans, Male, Middle Aged, Models, Molecular, Polycythemia, Procollagen-Proline Dioxygenase, Protein Conformation, Germ-Line Mutation, Amino Acid Substitution, Hypoxia-Inducible Factor-Proline Dioxygenases
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