title: Genetic and clinical heterogeneity of ferroportin disease.
abstract: Ferroportin is encoded by the SLC40A1 gene and mediates iron export from cells by interacting with hepcidin. SLC40A1 gene mutations are associated with an autosomal type of genetic iron overload described as haemochromatosis type 4, or HFE4 (Online Mendelian Inheritance in Man number 606069), or ferroportin disease. We report three families with this condition caused by novel SLC40A1 mutations. Denaturing high-performance liquid chromatography was employed to scan for the SLC40A1 gene. A D181V (A846T) mutation in exon 6 of the ferroportin gene was detected in the affected members of an Italian family and shown to have a de novo origin in a maternal germinal line. This mutation was associated with both parenchymal and reticuloendothelial iron overload in the liver, and with reduced urinary hepcidin excretion. A G80V (G543T) mutation in exon 3 was found in the affected members of an Italian family with autosomal hyperferritinaemia,. Finally, a G267D (G1104A) mutation was identified in exon 7 in a family of Chinese descent whose members presented with isolated hyperferritinaemia. Ferroportin disease represents a protean genetic condition in which the different SLC40A1 mutations appear to be responsible for phenotypic variability. This condition should be considered not only in families with autosomal iron overload or hyperferritinaemia, but also in cases of unexplained hyperferritinaemia.
authors.affiliation: Unit of Genomics for the Diagnosis of Human Pathologies, IRCCS H. San Raffaele, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cremonesi
authors.forename: Laura
authors.initials: L
authors.lastname: Cemonesi
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Forni
authors.forename: Nadia
authors.initials: N
authors.lastname: Soriani
authors.forename: Martina
authors.initials: M
authors.lastname: Lamagna
authors.forename: Isabella
authors.initials: I
authors.lastname: Fermo
authors.forename: Filomena
authors.initials: F
authors.lastname: Daraio
authors.forename: Anna
authors.initials: A
authors.lastname: Galli
authors.forename: Daniela
authors.initials: D
authors.lastname: Pietra
authors.forename: Luca
authors.initials: L
authors.lastname: Malcovati
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ferrari
authors.forename: Clara
authors.initials: C
authors.lastname: Camaschella
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
mesh_terms: D000293:Adolescent; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000652:urine; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D002681:China / Q000208:ethnology; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005293:Ferritins / Q000097:blood; D005838:Genotype; D006432:Hemochromatosis / Q000235:genetics* / Q000378:metabolism; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000032:analysis / Q000378:metabolism; D007558:Italy; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016415:Sequence Alignment; D000098742:Ferroportin
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C578702:HAMP protein, human; D064451:Hepcidins; D012333:RNA, Messenger; D000098742:Ferroportin; D005293:Ferritins; D007501:Iron