Beutler Ernest
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Annu Rev Med. 2006;57:331-47. doi: 10.1146/annurev.med.57.121304.131310.
A number of genetic disorders can result in the accumulation of excess iron in the body. These causes of hereditary hemochromatosis include defects in genes encoding HFE, transferrin receptor 2, ferroportin, hepcidin, and hemojuvelin. Hepcidin, with its cognate receptor, ferroportin, has emerged as a central regulator of iron homeostasis; all of the known causes of hemochromatosis appear to prevent this system from functioning normally. The most common form of primary hemochromatosis is that caused by C282Y mutation of the HFE gene. This mutation is most prevalent among Northern Europeans. Although the frequency of the homozygous genotype is approximately 5 per 1000, the disease itself is quite rare because the clinical penetrance of the genotype is very low.
许多遗传性疾病可导致体内铁过量蓄积。遗传性血色素沉着症的这些病因包括编码HFE、转铁蛋白受体2、铁转运蛋白、铁调素和血色素沉着蛋白的基因缺陷。铁调素与其同源受体铁转运蛋白已成为铁稳态的核心调节因子；所有已知的血色素沉着症病因似乎都阻止了该系统正常运作。原发性血色素沉着症最常见的形式是由HFE基因的C282Y突变引起的。这种突变在北欧人群中最为普遍。尽管纯合基因型的频率约为每1000人中有5人，但由于该基因型的临床外显率非常低，所以这种疾病本身相当罕见。
