A CANDIDATE GENE FOR HEMOCHROMATOSIS - FREQUENCY OF THE C282Y AND H63D MUTATIONS

The gene whose alteration causes hereditary hemochromatosis (HFE accor ding to the international nomenclature) was, more than 20 years ago, s hown to map to 6p21.3. It has since escaped all efforts to identify it by positional cloning strategies. Quite recently, a gene named HLA-H was reported as being responsible for the disease. Two missense mutati ons, Cys282Tyr (C282Y) and His63Asp (H63D), were observed, but no proo f was produced that the gene described is the hemochromatosis gene. To validate this gene as the actual site of the alteration causing hemoc hromatosis, we decided to look for the two mutations in 132 unrelated patients from Brittany. Our results indicate that more than 92% of the se patients are homozygous for the C282Y mutation, and that all 264 ch romosomes but 5 carry either mutation. These findings confirm the dire ct implication of HLA-H in hemochromatosis.