Chuvash-type congenital polycythemia in 4 families of Asian and Western European ancestry.
The Chuvash form of polycythemia is an autosomal recessive disorder common to a large number of families in central Russia. Affected individuals have been reported to be homozygous for an Arg200Trp mutation in the von Hippel-Lindau (VHL) gene. We have screened 78 patients with erythrocytosis and found 8 of Bangladeshi and Pakistani origin to be homozygous for the Arg200Trp mutation and another of English descent to be heterozygous. Of these patients, 5 have elevated serum erythropoietin (Epo) levels, while the other 4 have Epo values in the normal range. The heterozygous patient does not fulfill the Chuvash criterion for homozygosity of the Arg200Trp mutation and consequently may harbor a further, as yet uncharacterized, mutation. This mutation has a wider geographic distribution than originally presumed and haplotype analysis suggests a common origin of the Arg200Trp mutation in the 4 families, but it still remains to be established if it has arisen independently of the Chuvash population.
Percy
Melanie J
MJ
Department of Haematology, Floor C, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB, Northern Ireland. melanie.percy@bll.n-i.nhs.uk
McMullin
Mary Frances
MF
Jowitt
Simon N
SN
Potter
Michael
M
Treacy
Marilyn
M
Watson
William H
WH
Lappin
Terence R J
TR
D001208:Asia; D004921:Erythropoietin / Q000097:blood; D005060:Europe; D005192:Family Health; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011086:Polycythemia / Q000151:congenital* / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D025521:Tumor Suppressor Proteins; D004921:Erythropoietin; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human