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Hemochromatosis: a genetic defect in iron metabolism
Author(s) -
Jazwinska E. C.
Publication year - 1998
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/(sici)1521-1878(199807)20:7<562::aid-bies7>3.0.co;2-m
Subject(s) - hemochromatosis , missense mutation , hereditary hemochromatosis , mutant , beta 2 microglobulin , biology , gene , genetics , mutation , major histocompatibility complex , immunology
Hemochromatosis (HC), the common inherited disorder in iron metabolism, affects at least 1 in 300 Caucasians. The disorder causes inappropriately high iron absorption and accumulation of excess iron in the parenchymal cells of the major organs of the body. The gene responsible for HC has recently been cloned and is termed HFE; two missense mutations have been reported in the gene, both cause amino acid substitutions (H63D and C282Y), but to date only the C282Y mutation has been found to clearly correlate with HC in all affected populations. HFE is highly homologous to genes in the major histocompatibility complex (MHC) class I family; all of these genes encode a heterodimeric protein which is complexed to β 2 ‐microglobulin, a coupling essential for cell surface expression of a functional molecule. The first important step toward establishing the role of HFE in the pathogenesis of HC came with the recent observation that the C282Y mutation disrupts the binding of β 2 ‐microglobulin to the HFE protein and as a result the mutant molecule is not expressed on the cell surface. BioEssays 20: 562–568, 1998. © 1998 John Wiley & Sons Inc.