Von Hippel-Lindau-dependent polycythemia is endemic on the island of Ischia: identification of a novel cluster
Open accessAbstract
Chuvash polycythemia (MIM 263400) is an autosomal recessive disorder characterized by a high hemoglobin level, relatively high serum erythropoietin, and early death. It results from a Von Hippel-Lindau (VHL) gene mutation (C598T) that causes increased HIF-1alpha activity and erythrocyte production in the face of normoxia. This polycythemia is endemic in Chuvashia, whereas its worldwide frequency is very low. We investigated the incidence of the Chuvash-type VHL mutation in Campania (South Italy) and identified 14 affected subjects (5 families). Twelve live on the island of Ischia (Bay of Naples). From analysis of the mutated allele, we found that the disease was more frequent on Ischia (0.070) than in Chuvashia (0.057). The haplotype of all patients matched that identified in the Chuvash cluster, thereby supporting the single-founder hypothesis. We also found that nonaffected heterozygotes had increased HIF-1alpha activity, which might confer a biochemical advantage for mutation maintenance. In conclusion, we have identified the first large cluster of Chuvash erythrocytosis outside Chuvashia, which suggests that this familial polycythemia might be endemic in other regions of the world.
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Chuvash polycythemia is caused by a homozygous mutation in VHL at codon 200, R200W.
“It is caused by a homozygous mutation in the VHL tumor suppressor at codon 200, R200W”
From Regulation of erythropoiesis by hypoxia-inducible factors (2013) · cites this paper as [134]
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- Authors
- Perrotta, S., Nobili, B., Ferraro, M., Migliaccio, C., Borriello, A., Cucciolla, V., Martinelli, V., Rossi, F., Punzo, F., Cirillo, P., Parisi, G., Zappia, V., Rotoli, B., & Ragione, F. D.
- Affiliations
- University of Campania "Luigi Vanvitelli" (IT)
- From the Department of Pediatrics, Second University of Naples, Italy; the Department of Biochemistry and Biophysics “F. Cedrangolo,” Second University of Naples, Italy; the Division of Hematology, Federico II University, Naples, Italy; and the Divisione di Pediatria, Ospedale Anna Rizzoli, Lacco Ameno d'Ischia, Naples, Italy.
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-01-15
- Volume
- 107
- Issue
- 2
- Pages
- 514-519
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2112503706
- Cited by
- 93
- References
- 29
- Citations by year
- 2026: 2 · 2024: 4 · 2023: 1 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 2 · 2017: 3 · 2016: 4 · 2014: 3 · 2013: 7 · 2012: 6
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (other-oa)
- Funders
- Friedreich's Ataxia Research Alliance
- 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
- Chuvash polycythemia, von Hippel-Lindau gene, erythropoiesis, founder effect, haplotype analysis, endemic disease, Ischia, Chuvash Republic, autosomal recessive disorder, overdominance
- MeSH terms
- Adult, Hypoxia, Cell Line, Transformed, Child, DNA Mutational Analysis, Female, Geography, Haplotypes, Heterozygote, Homozygote, Humans, Italy, Lymphocytes, Male, Mutation, Pedigree, Polycythemia, Von Hippel-Lindau Tumor Suppressor Protein, Hypoxia-Inducible Factor 1, alpha Subunit
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