Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antimicrobial Cationic Peptides / genetics
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Antimicrobial Cationic Peptides / metabolism
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Cation Transport Proteins / genetics
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Cation Transport Proteins / metabolism
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GPI-Linked Proteins
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Hemochromatosis / classification
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Hemochromatosis / genetics*
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Hemochromatosis / metabolism
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Hemochromatosis Protein
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Hepcidins
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Histocompatibility Antigens Class I / genetics
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Homeostasis* / physiology
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Humans
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Iron / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mutation
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Receptors, Transferrin / genetics
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Receptors, Transferrin / metabolism
Substances
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Antimicrobial Cationic Peptides
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Cation Transport Proteins
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GPI-Linked Proteins
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HAMP protein, human
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HFE protein, human
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HJV protein, human
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Hamp protein, mouse
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Hemochromatosis Protein
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Hepcidins
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Histocompatibility Antigens Class I
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Membrane Proteins
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Receptors, Transferrin
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TFR2 protein, human
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metal transporting protein 1
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Iron