title: Expression of HLA-linked hemochromatosis in subjects homozygous or heterozygous for the C282Y mutation.
abstract: OBJECTIVE
  In the absence of a genetic test, diagnostic criteria for hereditary hemochromatosis have been imprecise. The identification of the HFE gene and the C282Y mutation allow definition of expression of this disease and reassessment of diagnostic criteria. The aim of this study was to analyze the concordance between the genetic diagnosis and the previous clinical diagnosis in families with hemochromatosis.
  
  
  METHODS
  Three hundred subjects were tested for the C282Y mutation and were grouped as homozygous, heterozygous, or homozygous normal.
  
  
  RESULTS
  All adults previously diagnosed as homozygous or heterozygous for HLA-linked hereditary hemochromatosis carried at least one C282Y mutation. Two adolescents, previously thought to be homozygous, had no C282Y mutation. Of 127 subjects homozygous for the mutation, 105 met criteria for diagnosis. Iron overload was not expressed in 6.7% of homozygous men and 32.7% of homozygous women. The iron indices in 8 of 171 subjects heterozygous for the C282Y mutation were within the range previously regarded as indicative of homozygosity. Seven of these 8 carried the H63D mutation.
  
  
  CONCLUSIONS
  In Australia, 17.3% of subjects homozygous for the C282Y mutation do not express iron overload to meet current diagnostic criteria of hemochromatosis. In subjects heterozygous for the mutation, 4.8% have iron overload in the range previously diagnosed as homozygous. Nonexpression is common, particularly in women.
authors.affiliation: Clinical Sciences Unit, Queensland Institute of Medical Research and University of Queensland, Brisbane, Australia.
authors.forename: D H
authors.initials: DH
authors.lastname: Crawford
authors.forename: E C
authors.initials: EC
authors.lastname: Jazwinska
authors.forename: L M
authors.initials: LM
authors.lastname: Cullen
authors.forename: L W
authors.initials: LW
authors.lastname: Powell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D008040:Genetic Linkage; D006680:HLA Antigens / Q000235:genetics*; D006432:Hemochromatosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000175:diagnosis / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012727:Sex Characteristics; D014168:Transferrin / Q000032:analysis
chemical_list: D006680:HLA Antigens; D014168:Transferrin