A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis
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DOI：
10.1038/ng0896-399
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发表时间：
1996-08-01
期刊：
影响因子：
30.8
通讯作者：
Wolff, RK
中科院分区：
文献类型：
--
作者：
Feder, JN;Gnirke, A;Wolff, RK
遗传性血色病（HH），其影响约1/400，并且具有估计的携带者频率为1/10的北方欧洲血统个体，导致由铁沉积增加引起的多器官功能障碍，并且如果早期发现是可治疗的。使用连锁不平衡和全单倍型分析，我们已经确定了一个250-组氨酸区域超过3兆碱基端粒的主要组织相容性复合体（MHC）是相同的，由下降85%的患者染色体。在这一区域内，我们已经确定了一个与MHC I类家族相关的基因，称为HLA-H，含有两个错义改变。其中一个被预测为与这类蛋白质结合，并且在178名患者中的83%中被发现是纯合子。该基因在血色病中的作用得到了主要突变的频率和性质的支持，并且先前的研究暗示了MHC I类蛋白参与铁代谢。
Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multiorgan dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.