title: Autosomal dominant iron overload due to a novel mutation of ferroportin1 associated with parenchymal iron loading and cirrhosis.
abstract: We report the identification of a novel mutation in ferroportin1 in an Australian family with autosomal dominant iron overload. The phenotype of iron overload in one member of this family is associated with high serum ferritin concentration and elevated transferrin saturation. The pattern of iron overload in the liver shows accumulation predominantly in parenchymal cells with some Kupffer cell iron loading. Although some cases of type 4 haemochromatosis have been associated with the development of liver fibrosis this is the first report of a patient with fully established cirrhosis at a relatively young age (32 years). The coexistence of sarcoidosis in this patient may contribute to the more severe phenotype. This report highlights the phenotypic variability that can occur in type 4 haemochromatosis. Some patients have predominant reticuloendothelial iron loading and normal transferrin saturation whereas others have predominant parenchymal iron loading and elevated transferrin saturation. The reasons for this variability remain to be determined. Interestingly this is the third mutation to affect asparagine 144, reinforcing the important role for this amino acid in the function of ferroportin1.
authors.affiliation: Membrane Transport Laboratory, The Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane, Qld 4006, Australia.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Wallace
authors.forename: Roslyn M
authors.initials: RM
authors.lastname: Clark
authors.forename: Hugh A J
authors.initials: HA
authors.lastname: Harley
authors.forename: V Nathan
authors.initials: VN
authors.lastname: Subramaniam
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005091:Exons; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D019190:Iron Overload / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D000098742:Ferroportin; D004247:DNA