title: Prevalence of C282Y and E168X HFE mutations in an Italian population of Northern European ancestry.
abstract: OBJECTIVE
  In Italy, the prevalence of C282Y is lower than in Northern European countries. We hypothesized a higher prevalence of C282Y in Northern than in Southern Italian populations. We previously identified a nonsense mutation (E168X) in hemochromatosis probands originating from a region in the north-west of Italy. We aimed to define the prevalence of C282Y and E168X in that region and the origin of the E168X mutation by haplotype analysis.
  
  
  METHODS
  Six-hundred and six blood donors were investigated for C282Y, H63D, S65C and E168X mutations by polymerase chain reaction (PCR)-restriction assays. Three hundred were also tested for rare HFE and TFR2 mutations by reverse-hybridization test strips. D6S265, D6S105 and D6S1281 microsatellites were analyzed to define E168X 6p-associated haplotypes.
  
  
  RESULTS
  One C282Y homozygote, thirteen C282Y/ H63D compound heterozygotes, four E168X heterozygotes and three E168X/H63D compound heterozygotes were found. The allele frequencies of C282Y, H63D, S65C, and E168X were 4.7%, 14.9%, 0.74% and 0.58%, respectively.
  
  
  CONCLUSIONS
  The prevalence of C282Y in the region investigated was much higher than that previously reported in Italy. This finding is probably due to the heavy Celtic component of this north-western population and suggests that in populations of Northern Italian descent screening studies for hemochromatosis could be cost-effective. The prevalence of E168X in this region, although low, suggests that the mutation probably originated here many years ago and its frequency increased as a result of a local founder effect. Given its severity, we suggest that the E168X mutation should be searched for in all hemochromatosis patients of Northern ancestry with an incomplete HFE genotype.
authors.affiliation: Clinica Medica, Ospedale San Gerardo, via Donizetti 106, 20052 Monza, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Salvioni
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mariani
authors.forename: Christian
authors.initials: C
authors.lastname: Oberkanins
authors.forename: Anne
authors.initials: A
authors.lastname: Moritz
authors.forename: Viviana
authors.initials: V
authors.lastname: Mauri
authors.forename: Sara
authors.initials: S
authors.lastname: Pelucchi
authors.forename: Alessia
authors.initials: A
authors.lastname: Riva
authors.forename: Cristina
authors.initials: C
authors.lastname: Arosio
authors.forename: Paolo
authors.initials: P
authors.lastname: Cerutti
authors.forename: Alberto
authors.initials: A
authors.lastname: Piperno
mesh_terms: D005260:Female; D005838:Genotype; D006239:Haplotypes; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology / Q000208:ethnology; D008297:Male; D008403:Mass Screening; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D015995:Prevalence; D019371:Topography, Medical
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins