Von Hippel-Lindau-dependent polycythemia is endemic on the island of Ischia: identification of a novel cluster.

@article{Perrotta2006VonHP,
  title={Von Hippel-Lindau-dependent polycythemia is endemic on the island of Ischia: identification of a novel cluster.},
  author={Silverio Perrotta and Bruno Nobili and Marcella Ferraro and Carmela Migliaccio and Adriana Borriello and Valeria Cucciolla and Vincenzo Martinelli and Francesca Rossi and Francesca Punzo and Paola Cirillo and Giuseppe Parisi and Vincenzo Zappia and Bruno Rotoli and Fulvio Della Ragione},
  journal={Blood},
  year={2006},
  volume={107 2},
  pages={
          514-9
        }
}
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… 
von Hippel-Lindau mutation in mice recapitulates Chuvash polycythemia via hypoxia-inducible factor-2alpha signaling and splenic erythropoiesis.
TLDR
It is suggested that enhanced expression of key HIF-2alpha genes promotes splenic erythropoiesis, resulting in the development of polycythemia in Vhl(R/R) mice.
The phenotype of polycythemia due to Croatian homozygous VHL (571C>G:H191D) mutation is different from that of Chuvash polycythemia (VHL 598C>T:R200W)
TLDR
It is shown that erythropoietin levels in homozygous VHL H191D individuals are higher than in VHL R200W patients of similar ages, and their native erythroid progenitors, unlike Chuvash R 200W, are not hypersensitive to erycythemia.
The heterozygote advantage of the Chuvash polycythemia VHLR200W mutation may be protection against anemia
TLDR
Heterozygosity for VHLR200W may provide protection from anemia; such protection could explain the persistence of this mutation.
CONGENITAL ERYTHROCYTOSIS ARE RARE DISORDERS WITH MANY GENES INVOLVED. FUNCTIONAL EVALUATION OF NOVEL PHD2 AND EPOR MUTATIONS.
TLDR
These are the first missense mutations of EPOR with a functional demonstrated activity that affect the EPOR signaling cascade that impair the C-terminal negative regulatory domain and determine gain-of-function in theEPOR signalling cascade.
Chuvash polycythemia VHLR200W mutation is associated with down-regulation of hepcidin expression.
TLDR
Up-regulation of the hypoxic response leads to decreased expression of hepcidin that may be independent of increased erythropoietin levels and increased RBC counts.
downregulation of hepcidin expression mutation is associated with R200W VHL Chuvash polycythemia
TLDR
In univariate analyses, serum hepcidin concentration correlated positively with serum ferritin concentration and negatively with homozygosity for VHL R200W, the master regulator of iron metabolism.
First familial cases of type 2 congenital erythrocytosis (ECYT2) with a Chuvash pathogenic variant in VHL gene in Poland: example of the clinical utility of next-generation sequencing in diagnostics of orphan diseases
TLDR
These are the first confirmed cases of familial erythrocytosis type 2, also known as Chuvash type, in Poland, reported in two siblings, a 2-year-old boy and his younger sister.
Increased size of solid organs in patients with Chuvash polycythemia and in mice with altered expression of HIF-1α and HIF-2α
TLDR
In addition to increased red cell mass, the sizes of liver, spleen, and kidneys are increased in Chuvash polycythemia, suggesting that, at least in the liver, this phenotype may result from increased HIF-2α and decreased p21Cip1 levels leading to increased hepatocyte proliferation.
polycythemia but not with cancer mutation in exon 2 is associated with congenital VHL Novel homozygous
TLDR
A new homozygous VHL exon 2 mutation of the VHL gene, P138L, is described, which is associated in the affected homozygote with congenital polycythemia but not in her, or her heterozygous relatives, with cancer or other VHL syndrome tumors.
Thrombocythemia and polycythemia in patients younger than 20 years at diagnosis: clinical and biologic features, treatment, and long-term outcome.
TLDR
After a median follow-up of 124 months, no patient had developed leukemia or myelofibrosis and 5% had thrombosis; the miscarriage rate in thromBocythemic patients was 14%.
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