title: Detection of hereditary haemochromatosis in an HLA-identical pedigree showing discordance between HLA class I genes and the disease locus.
abstract: Hereditary haemochromatosis is a recessive disease in which primary hepatocellular carcinoma, complicating cirrhosis, is responsible for about one-third of deaths in affected homozygotes. We describe a unique HLA haplo-identical pedigree showing parent-to-offspring transmission of hereditary haemochromatosis in whom HLA typing studies, including class I and class II allogenotype analysis, were of no benefit in identifying affected homozygotes. However, affected siblings in the pre-cirrhotic stage of haemochromatosis, with apparent discordance between the haemochromatosis allele and class I loci on chromosome 6, were detected by undertaking a family study, using analysis of serum parameters of iron status in combination with magnetic resonance imaging (MRI). This pedigree emphasises the critical importance of genetic and non-invasive methods for the identification of asymptomatic homozygotes before cirrhosis develops.
authors.affiliation: Department of Haematology, Royal Postgraduate Medical School, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Dokal
authors.forename: D
authors.initials: D
authors.lastname: Lord
authors.forename: D
authors.initials: D
authors.lastname: Rhodes
authors.forename: G
authors.initials: G
authors.lastname: Bydder
authors.forename: T
authors.initials: T
authors.lastname: Cox
mesh_terms: D000483:Alleles; D015139:Blotting, Southern; D002896:Chromosomes, Human, Pair 6; D005260:Female; D005805:Genes, MHC Class I; D008040:Genetic Linkage / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics; D006432:Hemochromatosis / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000097:blood; D008099:Liver / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010375:Pedigree
chemical_list: D006680:HLA Antigens; D007501:Iron