A candidate gene for hemochromatosis : frequency of the C282Y and H63D mutations

• Published in: Human genetics Vol. 100; no. 5-6; pp. 544 - 547
• Main Authors: JOUANOLLE, A. M, FERGELOT, P, GANDON, G, YAOUANQ, J, LE GALL, J. Y, DAVID, V
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01-10-1997; Berlin; New York, NY
• Subjects: Biological and medical sciences; Chromosomes, Human, Pair 6 - genetics; France; Gene Frequency; Genes, MHC Class I - genetics; Haplotypes; Hemochromatosis - genetics; Hemochromatosis Protein; Heterozygote; Histocompatibility Antigens Class I - genetics; HLA Antigens - genetics; Homozygote; Humans; Medical sciences; Membrane Proteins; Metabolic diseases; Metals (hemochromatosis...); Mutation - genetics; Other metabolic disorders; Human; Hemochromatosis; Pigments; Metabolic diseases; Genetics; Iron; Mutation; Enzymopathy; Genetic disease
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s004390050549

The gene whose alteration causes hereditary hemochromatosis (HFE according to the international nomenclature) was, more than 20 years ago, shown 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 mutations, Cys282Tyr (C282Y) and His63Asp (H63D), were observed, but no proof was produced that the gene described is the hemochromatosis gene. To validate this gene as the actual site of the alteration causing hemochromatosis, we decided to look for the two mutations in 132 unrelated patients from Brittany. Our results indicate that more than 92% of these patients are homozygous for the C282Y mutation, and that all 264 chromosomes but 5 carry either mutation. These findings confirm the direct implication of HLA-H in hemochromatosis.