title: Prevalence and clinical significance of HFE gene mutations in patients with iron overload.
abstract: OBJECTIVE
  The HFE gene contains two mutant alleles; C282Y and H63D. The C282Y mutation occurs in 55-100% of patients with hereditary hemochromatosis. The aim of our study was to re-examine the frequencies of the C282Y and H63D mutations in patients with mild and marked iron overload and in normal subjects.
  
  
  METHODS
  A total of 82 patients with iron overload were included in this study and had hepatic iron index determination and/or quantitation of iron stores by phlebotomy. The control group consisted of 81 healthy blood donors. HFE mutation analysis was performed on leukocyte DNA using PCR-amplified genomic DNA.
  
  
  RESULTS
  Of patients with iron overload, 70/82 (85%) were homozygous for C282Y versus 2/81 (2.5%) in the control population. Four patients had no HFE mutations despite significant iron overload, including a sister and brother (brother not included in the study group) with hepatic iron concentrations >500 micromoles/g dry weight.
  
  
  CONCLUSIONS
  In all, 85% of our patients with iron overload were C282Y homozygotes, although a few had no HFE gene mutations. Pooled data and analysis of chromosomes considered to be at risk for H63D indicate that H63D is associated with iron overload.
authors.affiliation: Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Brandhagen
authors.forename: V F
authors.initials: VF
authors.lastname: Fairbanks
authors.forename: W P
authors.initials: WP
authors.lastname: Baldus
authors.forename: C I
authors.initials: CI
authors.lastname: Smith
authors.forename: K E
authors.initials: KE
authors.lastname: Kruckeberg
authors.forename: D J
authors.initials: DJ
authors.lastname: Schaid
authors.forename: S N
authors.initials: SN
authors.lastname: Thibodeau
mesh_terms: D000368:Aged; D000483:Alleles; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged
chemical_list: C103673:HFE protein, human; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins