title: G80S-linked ferroportin disease: classical ferroportin disease in an Asian family and reclassification of the mutant as iron transport defective.
abstract: OBJECTIVE
  Hereditary iron overload associated with mutations in the ferroportin gene produces a dichotomy of phenotypes resulting from either increase or decrease in iron efflux capacity. In this study, we examined the molecular basis of iron overload in a family of Vietnamese origin, characterized the molecular and cellular defect, and correlated it with the clinical and pathological phenotype.
  
  
  METHODS
  We analyzed the ferroportin gene by DNA sequencing. The molecular characterization was performed by immunofluorescence microscopy analysis of transfected cells. We analyzed ferritin levels, in cells expressing wild-type and mutant ferroportin, to define the nature of the molecular defect in iron transport.
  
  
  RESULTS
  We identified a G to A nucleotide change at position 238 in the ferroportin gene leading to the G80S substitution. Cellular analysis of the mutant protein indicates that this amino acid change does not affect the localization of the protein but does affect its ability to transport iron.
  
  
  CONCLUSIONS
  The G80S mutation results in a mutated ferroportin associated with iron overload and is predicted to be defective in iron export.
authors.affiliation: Membrane Transport Laboratory, Division of Cancer and Cell Biology, Queensland Institute of Medical Research, Herston, Queensland, Australia.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: McDonald
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Wallace
authors.forename: Lesa
authors.initials: L
authors.lastname: Ostini
authors.forename: Sally J
authors.initials: SJ
authors.lastname: Bell
authors.forename: Barbara
authors.initials: B
authors.lastname: Demediuk
authors.forename: V Nathan
authors.initials: VN
authors.lastname: Subramaniam
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D019915:DNA Primase / Q000235:genetics; D005260:Female; D005293:Ferritins / Q000378:metabolism; D056726:Genetic Association Studies; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D050505:Mutant Proteins / Q000235:genetics* / Q000378:metabolism*; D020125:Mutation, Missense; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014744:Vietnam / Q000208:ethnology; D055815:Young Adult; D000098742:Ferroportin
chemical_list: D027682:Cation Transport Proteins; D050505:Mutant Proteins; D011994:Recombinant Proteins; D000098742:Ferroportin; D005293:Ferritins; D007501:Iron; D019915:DNA Primase