A PCR-SSP METHOD FOR DETECTING THE HIS63ASP MUTATION IN THE HFE GENE ASSOCIATED WITH HEREDITARY HEMOCHROMATOSIS

Hereditary haemochromatosis is an autosomal recessive disease in which there is defective regulation of iron absorption, causing gradual acc umulation of excessive amounts of iron in certain organs. Recently, a candidate gene for hereditary haemochromatosis has been identified, lo cated on the short arm of chromosome 6, telomeric to the major histoco mpatibility complex (MHC) and showing sequence homology to the human l eucocyte antigen (HLA) class I genes. Two mutations have been found in this gene that are potential markers for haemochromatosis. The first, a cysteine to tyrosine substitution (Cys282Tyr) is strongly associate d with the disease, whereas the second mutation, a histidine to aspart ic acid substitution (His63Asp) shows a less obvious relation. To exam ine the importance of this second mutation in hereditary haemochromato sis it is important to study the links between this genotype and abnor malities of iron metabolism. A polymerase chain reaction method using sequence specific primers is described which might be useful for ident ifying those individuals carrying the mutation that encodes the His63A sp substitution, who might be at risk from a milder form of haemochrom atosis.