Frequency of HFE gene mutations and genotype-phenotype correlations in Swiss patients with hereditary haemochromatosis

Hereditary haemochromatosis is one of the most common genetic disorders aff ecting populations of European ancestry. Isolation of a strong candidate ge ne, the HFE gene, allows genetic diagnosis in a large number of cases. Howe ver, different mutation frequencies have been reported in hereditary haemoc hromatosis patient populations from various geographic regions. Such data a nd phenotype-genotype correlations from Swiss patients with hereditary haem ochromatosis are lacking. The objective of our study was to determine the f requency of HFE gene mutations in Swiss patients with hereditary haemochrom atosis and to describe the clinical phenotype of patients with either a hom ozygous C282Y mutation or compound heterozygotes. 71 patients with a clinical diagnosis of hereditary haemochromatosis were i dentified through a questionnaire sent to physicians caring for hereditary haemochromatosis patients. Pertinent clinical data, in particular those ref lecting iron body stores, were collected. Genotyping for the C282Y and H63D mutation of the HFE gene was performed. In 90% of the cases a mutation of the HFE gene was found. 86% of the patien ts were homozygous for the C282Y mutation, 4% were compound heterozygotes f or the C282Y and the H63D mutation. Patients with the homozygous C282Y muta tion showed a broad phenotypic spectrum that could not be accounted for by age or sex differences only. Our results demonstrate that within the Swiss population genetic testing, c an also identify the vast majority of patients with hereditary haemochromat osis. However, the diagnosis is not ruled out by a negative genetic test. F urthermore, a broad phenotypic spectrum is associated with the homozygous C 282Y mutation in Swiss hereditary haemochromatosis patients. The implicatio ns of these findings for planning of widespread genetic screening for hered itary haemochromatosis in the general population are discussed.