THE HEMOCHROMATOSIS GENE - MOLECULAR ANALYSIS - APPLICATIONS FOR DIAGNOSIS

Hemochromatosis is the most common single gene disorder in Caucasian p opulations. Regulation of iron balance by intestine is impaired, leadi ng to a widespread deposition of iron, and the disease is associated w ith an increased risk of hepatocellular carcinoma. Typically the exces s of iron treated by phlebotomies is performed in our Blood Center. In 1996 an original paper identifying HFE as a strong candidate gene for hemochromatosis was published and two mutations were described (C282Y and H63D). The former results in a cysteine to tyrosine substitution at amino acid 282 and was found in different patient populations up to 80-90% of patients homozygous for the C282Y mutation. The frequency o f the second variant H63D is also increased in hemochromatosis patient s but its penetrance is probably not complete. Assessing clinical impl ications is a new way of identifying patients at risk for this frequen t and probably underdiagnosed disease, and important because treatment by venesections is safe with a proven benefit in preventing developme nt of the disease. Four hundred and eighty patients were included in o ur study and we have shown in this work a correlation between the geno type and the phenotypic presentation of the disorder, with patients ho mozygous for the C282Y mutation having a greater excess of iron. (C) 1 998 Elsevier, Paris.