title: Analysis of HFE and TFR2 mutations in selected blood donors with biochemical parameters of iron overload.
abstract: OBJECTIVE
  Hereditary hemochromatosis is a recessive condition characterized by iron accumulation in several organs, followed by organ damage and failure. The disorder is prevalently due to C282Y and H63D mutations in the HFE gene, but additional HFE and TFR2 mutations have been reported. Early iron overload may be assessed by biochemical parameters such as increased transferrin saturation and serum ferritin.
  
  
  METHODS
  Taking advantage of the collection of 178 DNA samples selected for increased transferrin saturation (>50% in males and >45% in females) from a previous large scale screening of Italian blood donors, we simultaneously assessed the presence of 14 hemochromatosis-associated molecular defects (11 of HFE and 3 of TFR2) by a reverse hybridization-based strip assay.
  
  
  RESULTS
  In the series studied the overall C282Y allele frequency was 9% and that of the H63D and S65C was 22.2% and 1.4%, respectively. One rare HFE allele (E168Q), but no TFR2 mutation was detected. When checked at a second examination, transferrin saturation was significantly higher in C282Y homozygotes, H63D/ C282Y compound heterozygotes and H63D homozygotes as compared to wild-type subjects (p<0.05).
  
  
  CONCLUSIONS
  Our results confirm previous findings on C282Y and H63D mutations in Italy, show that the C282Y allele frequency is enriched in samples selected for altered iron parameters, and that a few rare genotypes are present in Northern Italy. None of the known TFR2 mutations was identified in this series confirming the preliminary indication of their rare occurrence. Subjects with hemochromatosis-associated genotypes show a persistently higher mean transferrin saturation than do those with wild type genotypes.
authors.affiliation: Department of Clinical and Biological Sciences, ASO San Luigi, University of Torino, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Gobbi
authors.forename: Filomena
authors.initials: F
authors.lastname: Daraio
authors.forename: Christian
authors.initials: C
authors.lastname: Oberkanins
authors.forename: Anne
authors.initials: A
authors.lastname: Moritz
authors.forename: Fritz
authors.initials: F
authors.lastname: Kury
authors.forename: Gemino
authors.initials: G
authors.lastname: Fiorelli
authors.forename: Clara
authors.initials: C
authors.lastname: Camaschella
mesh_terms: D001782:Blood Donors; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000235:genetics*; D007558:Italy / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D017720:Molecular Epidemiology; D011990:Receptors, Transferrin / Q000235:genetics*
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human