Hemochromatosis mutations C282Y and H63D in 'cis' phase

Homozygosity for the C282Y mutation of the HFE gene is a highly significant risk factor for the development of hereditary hemochromatosis (HH) and the majority of patients with HH have this genotype. An Irish/Belgian female w ith an elevated serum ferritin level and a family history of hemochromatosi s was tested for the presence of the C282Y and H63D mutations. Results of d igested PCR products have shown the patient to be homozygous for C282Y muta tion and heterozygous for H63D mutation. Sequencing confirmed these finding s. Genotyping of the patient's offspring and husband has also indicated the inheritance of both C282Y and H63D in 'cis'. Implications of this finding are: 1) the compound heterozygous state is by far the most common, but not the universal. phase for individuals found to be heterozygous for the two m utations, C282Y and H63D, 2) the C282Y and H63D mutations in the 'cis' phas e may account for some cases of questionable parentage.