title: Frequency of the HFE C282Y and H63D mutations in Danish patients with clinical haemochromatosis initially diagnosed by phenotypic methods.
abstract: OBJECTIVE
  To assess the frequency of the C282Y and H63D mutations on the HFE gene in Danish patients with clinical hereditary haemochromatosis initially diagnosed by phenotypic methods.
  
  
  METHODS
  In the period 1950-1985, an epidemiological survey in Denmark identified 179 patients with clinical idiopathic haemochromatosis diagnosed by phenotypic methods (serum transferrin saturation, serum ferritin, liver biopsy and mobilisable body iron stores). In 32 unrelated patients, frozen blood samples were available for genetic analysis. In a subsequent series of 26 unrelated Danish patients, a phenotypic diagnosis of clinical idiopathic haemochromatosis was made before blood samples were taken for HFE genotyping. The total series consisted of 58 patients (40 men and 18 women) with a median age of 60 yrs (range 18-74). HFE genotyping was performed by the polymerase chain reaction (PCR) technique.
  
  
  RESULTS
  Among the patients, 55 of 58 (94.8%) were C282Y/C282Y homozygous. One 63-year-old woman (1.7%) was compound C282Y/H63D heterozygous. Two women (3.4%), aged 42 and 43 yrs were negative for both the C282Y and the H63D mutation.
  
  
  CONCLUSIONS
  In the Danish population, homozygosity for the C282Y mutation appears to be the prevailing cause of clinically overt genetic haemochromatosis. This finding has implications both for the evaluation of patients with iron overload disorders and for the strategy in future population screening surveys.
authors.affiliation: Department of Medicine B, Rigshospitalet, University of Copenhagen, Denmark. milman@rh.dk
authors.forename: Nils
authors.initials: N
authors.lastname: Milman
authors.forename: Pernille
authors.initials: P
authors.lastname: Koefoed
authors.forename: Palle
authors.initials: P
authors.lastname: Pedersen
authors.forename: Finn Cilius
authors.initials: FC
authors.lastname: Nielsen
authors.forename: Hans
authors.initials: H
authors.lastname: Eiberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003718:Denmark; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006432:Hemochromatosis / Q000175:diagnosis* / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins