title: Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene and VHL-haplotype analysis in patients with presumable congenital erythrocytosis.
abstract: OBJECTIVE
  Congenital erythrocytoses or polycythemias are rare and heterogeneous. A homozygous mutation (C598T->Arg200Trp) in the von Hippel-Lindau (VHL) gene was originally identified as the cause of the endemic Chuvash polycythemia. Subsequently this and other mutations in the VHL gene were also detected in several patients of different ethnic origin. Haplotype analyses of the VHL gene suggested a common origin for the Chuvash-type mutation.
  
  
  METHODS
  Thirty-four patients with presumable congenital erythrocytosis due to an unknown underlying disorder were examined for VHL gene mutations and VHL region haplotypes.
  
  
  RESULTS
  Four patients were homozygous and one patient heterozygous for the Chuvash-type mutation. One additional patient presented a previously not described heterozygous mutation G311->T VHL in exon 1. The haplotype analyses were in agreement with recently published data for three of the four patients with homozygous mutations as well as for the patient with a heterozygous Chuvash-type mutation. One patient of Turkish origin with homozygous Chuvash-type mutation had a haplotype not previously found in individuals with Chuvash-type mutation.
  
  
  CONCLUSIONS
  These results confirm that mutations in the VHL gene are responsible for a substantial proportion of patients with congenital erythrocytoses. Erythrocytoses due to a C598->T mutation of the VHL gene are not geographically restricted. The majority of patients with Chuvash polycythemia share a common VHL gene haplotype. The different haplotype in one of the patients with Chuvash-type mutation indicates that this mutation was not spread only from a single founder but developed independently in other individuals.
authors.affiliation: Dept. of Pediatrics, University Hospital Ulm, Prittwitzstrasse 43 D-89075 Ulm, Germany. holger.cario@medizin.uni-ulm.de
authors.forename: Holger
authors.initials: H
authors.lastname: Cario
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.forename: Norbert
authors.initials: N
authors.lastname: Jorch
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kyank
authors.forename: Petro E
authors.initials: PE
authors.lastname: Petrides
authors.forename: Dominik T
authors.initials: DT
authors.lastname: Schneider
authors.forename: Renate
authors.initials: R
authors.lastname: Uhle
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kohne
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004921:Erythropoietin / Q000097:blood; D005192:Family Health; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D017354:Point Mutation; D011086:Polycythemia / Q000151:congenital* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D006623:von Hippel-Lindau Disease / Q000235:genetics*
chemical_list: D004921:Erythropoietin