Jazwinska E C
Queensland Institute of Medical Research, Brisbane, Australia.
Bioessays. 1998 Jul;20(7):562-8. doi: 10.1002/(SICI)1521-1878(199807)20:7<562::AID-BIES7>3.0.CO;2-M.
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 beta 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 beta 2-microglobulin to the HFE protein and as a result the mutant molecule is not expressed on the cell surface.
血色素沉着症（HC）是铁代谢中常见的遗传性疾病，在每300名白种人中至少有1人受其影响。该疾病导致铁吸收异常增高，过量的铁在身体主要器官的实质细胞中蓄积。导致HC的基因最近已被克隆，称为HFE；该基因已报道有两个错义突变，均导致氨基酸替代（H63D和C282Y），但迄今为止，仅发现C282Y突变在所有受影响人群中都与HC有明确关联。HFE与主要组织相容性复合体（MHC）I类家族中的基因高度同源；所有这些基因都编码一种异二聚体蛋白，该蛋白与β2-微球蛋白复合，这是功能性分子在细胞表面表达所必需的结合。最近观察到C282Y突变破坏了β2-微球蛋白与HFE蛋白的结合，结果突变分子不在细胞表面表达，这是确定HFE在HC发病机制中作用的第一个重要步骤。
