New insights into iron homeostasis through the study of non-HFE hereditary haemochromatosis.
Non-HFE haemochromatosis is a negative definition applied to all those haemochromatosis disorders that are unrelated to HFE mutations. Four genes are responsible for the distinct types of non-HFE haemochromatosis: hepcidin and hemojuvelin are the genes involved in type 2 or juvenile haemochromatosis, transferrin receptor 2 is involved in type 3 haemochromatosis, and ferroportin 1 is mutated in type 4, the atypical dominant form of primary iron overload. Molecular genetic studies of these conditions have greatly contributed to our understanding of the regulation of iron absorption. A milestone was the discovery that hepcidin, the key iron regulator in mice, is the gene mutated in the most severe, juvenile form of haemochromatosis. This finding indicates a fundamental role of hepcidin in inhibiting both iron absorption from duodenal cells and iron release from macrophages, and has opened up a new view of haemochromatosis as a disorder of hepcidin.
Roetto
Antonella
A
Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Azienda Ospedaliera San Luigi Gonzaga, Regione Gonzole, 10, 10043 Orbassano, Torino, Italy.
Camaschella
Clara
C
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins; D006432:Hemochromatosis / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D058851:GPI-Linked Proteins; C578702:HAMP protein, human; C103673:HFE protein, human; C481006:HJV protein, human; C579599:Hamp protein, mouse; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D000098742:Ferroportin; D007501:Iron