title: A PCR-SSP method for detecting the His63Asp mutation in the HFE gene associated with hereditary haemochromatosis.
abstract: Hereditary haemochromatosis is an autosomal recessive disease in which there is defective regulation of iron absorption, causing gradual accumulation of excessive amounts of iron in certain organs. Recently, a candidate gene for hereditary haemochromatosis has been identified, located on the short arm of chromosome 6, telomeric to the major histocompatibility complex (MHC) and showing sequence homology to the human leucocyte 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 associated with the disease, whereas the second mutation, a histidine to aspartic acid substitution (His63Asp) shows a less obvious relation. To examine the importance of this second mutation in hereditary haemochromatosis it is important to study the links between this genotype and abnormalities of iron metabolism. A polymerase chain reaction method using sequence specific primers is described which might be useful for identifying those individuals carrying the mutation that encodes the His63Asp substitution, who might be at risk from a milder form of haemochromatosis.
authors.affiliation: Histocompatibility Laboratory, National Blood Service (Trent Centre), Sheffield, UK.
authors.forename: D
authors.initials: D
authors.lastname: Smillie
mesh_terms: D019943:Amino Acid Substitution; D001224:Aspartic Acid / Q000235:genetics; D002896:Chromosomes, Human, Pair 6; D017931:DNA Primers; D004587:Electrophoresis, Agar Gel; D005820:Genetic Testing / Q000379:methods*; D006432:Hemochromatosis / Q000175:diagnosis / Q000235:genetics*; D006639:Histidine / Q000235:genetics; D006801:Humans; D017354:Point Mutation; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D001224:Aspartic Acid; D006639:Histidine