title: Rapid and simple determination of hereditary haemochromatosis mutations by multiplex PCR-SSCP: detection of a new polymorphic mutation.
abstract: Hereditary haemochromatosis is a common inherited disorder leading to excessive accumulation of iron in various organs. Two missense substitutions at the HFE-gene have recently been associated with the disease, 187C G and 845G-->A (mutations H63D and C282Y, respectively). We present a simple, rapid PCR-SSCP multiplex screening method allowing the simultaneous detection of both substitutions. Furthermore, testing the method on 420 Danish blood donors revealed the presence of a hitherto undetected third substitution in 13 individuals. The new substitution, a 193A-->T transversion, affects codon 65 changing the code for serine to that of cysteine (S65C). It may thus have functional consequences for the HLA class protein encoded by the HFE-gene. The allele frequencies observed were: H63D 14.8%, C282Y 6.2% and S65C 1.5%, which for the two former alleles are in agreement with frequencies reported for other North European population samples.
authors.affiliation: Department of Pathology, Roskilde County Hospital, Denmark. evaberg@post11.tele.dk
authors.forename: K
authors.initials: K
authors.lastname: Simonsen
authors.forename: J
authors.initials: J
authors.lastname: Dissing
authors.forename: L
authors.initials: L
authors.lastname: Rudbeck
authors.forename: M
authors.initials: M
authors.lastname: Schwartz
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods*; D006432:Hemochromatosis / Q000235:genetics*; D006801:Humans; D007223:Infant; D009154:Mutation; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D004247:DNA