Genetic hemochromatosis and the HFE gene

The discovery of the HFE gene has lead to considerable improvement in the u nderstanding and the management of genetic hemochromatosis. More than 90 % of well-defined patients are homozygous for the C282 Y mutation, and geneti c testing has become an important diagnostic tool. The significance of the other mutations in the HFE gene remain controversial : only C282Y / H63D co mpound heterozygotes could present with a phenotype compatible with hemochr omatosis, but with a mild expression and a low penetrance. The link between iron overload and HFE mutation is explained by the interaction between HFE protein, beta-2-microglobulin and transferrin receptor; which is abolished by the C282Y mutation, but is not yet fully understood.