title: Heterozygous recipient and donor HFE mutations associated with a hereditary haemochromatosis phenotype after liver transplantation.
abstract: We observed the development of phenotypic hereditary haemochromatosis in a non-hereditary haemochromatosis liver transplant recipient, following transplantation with a liver from a C282Y heterozygous donor. No cause for secondary iron overload was identified. Subsequent sequencing of the HFE gene of both donor and recipient revealed a strong candidate for a novel pathogenic HFE mutation. In the recipient, heterozygosity for a single base substitution in exon 1, g.18 G>C, resulting in the substitution of arginine by serine at codon 6 (R6S), was detected. This R6S variation is likely to represent a novel pathogenic missense mutation of the HFE gene. An interaction between R6S heterozygosity in the recipient and C282Y heterozygosity in the donor liver is the most likely explanation for the development of iron overload in this patient. The report suggests that an hepatic defect is required for expression of hereditary haemochromatosis and that the intestinal HFE genotype is not the exclusive determinant of iron status. It also raises the possibility that a hereditary haemochromatosis phenotype may result from transplantation of C282Y heterozygous donor livers into recipients with heterozygous pathogenic HFE mutations. This possibility may have significant implications for the common practice of transplanting C282Y heterozygous livers.
authors.affiliation: Department of Gastroenterology and Hepatology, Flinders Medical Centre, Adelaide, South Australia, Australia. alan.wigg@flinders.edua.u
authors.forename: A J
authors.initials: AJ
authors.lastname: Wigg
authors.forename: H
authors.initials: H
authors.lastname: Harley
authors.forename: G
authors.initials: G
authors.lastname: Casey
mesh_terms: D000328:Adult; D001483:Base Sequence; D005260:Female; D006432:Hemochromatosis / Q000209:etiology* / Q000235:genetics; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins