title: Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3).
abstract: We describe a family with autosomal dominant inheritance of increased body iron stores characterized by raised serum ferritin concentration and normal transferrin saturation. Liver biopsy showed iron deposition in Kupffer cells without fibrosis. The clinical features of HFE-related hemochromatosis were absent, as were the Cys282Tyr and His63Asp mutations. Venesection therapy was poorly tolerated, suggesting a defect in iron release from reticuloendothelial stores. A 3-base pair deletion in exon 5 of the ferroportin 1 gene (SLC11A3) predicting Val162 deletion was found in affected members, but not in unaffected individuals or in 100 control subjects. Consensus structural predictions of the transmembrane helices showed that the deletion is in the extracellular loop between the third and fourth predicted transmembrane helices and lies within a spatial cluster of other known ferroportin 1 mutations. These results indicate that this extracellular cluster is functionally important for iron transport, and its disruption leads to iron overload.
authors.affiliation: Department of Haematology, Princess of Wales Hospital, Bridgend, United Kingdom.
authors.forename: Vinod
authors.initials: V
authors.lastname: Devalia
authors.forename: Kymberley
authors.initials: K
authors.lastname: Carter
authors.forename: Ann P
authors.initials: AP
authors.lastname: Walker
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Perkins
authors.forename: Mark
authors.initials: M
authors.lastname: Worwood
authors.forename: Alison
authors.initials: A
authors.lastname: May
authors.forename: James S
authors.initials: JS
authors.lastname: Dooley
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics*; D005192:Family Health; D005260:Female; D005293:Ferritins / Q000097:blood; D005799:Genes, Dominant; D006801:Humans; D019190:Iron Overload / Q000235:genetics*; D007728:Kupffer Cells / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D012157:Mononuclear Phagocyte System / Q000378:metabolism / Q000473:pathology*; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D000098742:Ferroportin; D005293:Ferritins