Department of Neurology and Neurobiology of Ageing, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa, Japan.
Brain. 2010 Oct;133(10):3043-57. doi: 10.1093/brain/awq216. Epub 2010 Sep 20.
We analysed the epidemiological data and clinical features of patients with prion diseases that had been registered by the Creutzfeldt-Jakob Disease Surveillance Committee, Japan, over the past 10 years, since 1999. We obtained information on 1685 Japanese patients suspected as having prion diseases and judged that 1222 patients had prion diseases, consisting of definite (n=180, 14.7%) and probable (n=1029, 84.2%) cases, except for dura mater graft-associated Creutzfeldt-Jakob disease which also included possible cases (n=13, 1.1%). They were classified into 922 (75.5%) with sporadic Creutzfeldt-Jakob disease, 216 (17.7%) with genetic prion diseases, 81 (6.6%) with acquired prion diseases, including 80 cases of dura mater graft-associated Creutzfeldt-Jakob disease and one case of variant Creutzfeldt-Jakob disease, and three cases of unclassified Creutzfeldt-Jakob disease (0.2%). The annual incidence rate of prion disease ranged from 0.65 in 1999 to 1.10 in 2006, with an average of 0.85, similar to European countries. Although methionine homozygosity at codon 129 polymorphism of the prion protein gene was reported to be very common (93%) in the general Japanese population, sporadic Creutzfeldt-Jakob disease in Japan was significantly associated with codon 129 homozygosity (97.5%), as reported in western countries. In sporadic Creutzfeldt-Jakob disease, MM1 type (Parchi's classification) is the most common, as in western countries. Among atypical sporadic Creutzfeldt-Jakob disease cases, the MM2 type appeared most common, probably related to the very high proportion of methionine allele in the Japanese population. As for iatrogenic Creutzfeldt-Jakob disease, only dura mater graft-associated Creutzfeldt-Jakob disease cases were reported in Japan and, combined with the data from previous surveillance systems, the total number of dura mater graft-associated Creutzfeldt-Jakob disease was 138, comprising the majority of worldwide dura mater graft-associated Creutzfeldt-Jakob disease patients. Regarding genetic prion diseases, the most common mutation of prion protein gene was V180I (41.2%), followed by P102L (18.1%), E200K (17.1%) and M232R (15.3%), and this distribution was quite different from that in Europe. In particular, V180I and M232R were quite rare mutations worldwide. Patients with V180I or M232R mutations rarely had a family history of prion diseases, indicating that a genetic test for sporadic cases is necessary to distinguish these from sporadic Creutzfeldt-Jakob disease. In conclusion, our prospective 10-year surveillance revealed a frequent occurrence of dura mater graft-associated Creutzfeldt-Jakob disease, and unique phenotypes of sporadic Creutzfeldt-Jakob disease and genetic prion diseases related to the characteristic distribution of prion protein gene mutations and polymorphisms in Japan, compared with those in western countries.
我们分析了自 1999 年以来，日本 Creutzfeldt-Jakob 病监测委员会登记的过去 10 年中 1685 例朊病毒病患者的流行病学数据和临床特征。我们获得了 1222 例日本朊病毒病疑似患者的信息，并判断其中 180 例（14.7%）为确诊病例，1029 例（84.2%）为可能病例，除外硬脑膜移植相关性 Creutzfeldt-Jakob 病（1.1%），包含可能病例。它们分为 922 例（75.5%）散发性 Creutzfeldt-Jakob 病、216 例（17.7%）遗传性朊病毒病、81 例（6.6%）获得性朊病毒病，包括 80 例硬脑膜移植相关性 Creutzfeldt-Jakob 病和 1 例变异 Creutzfeldt-Jakob 病，3 例未分类 Creutzfeldt-Jakob 病（0.2%）。朊病毒病的年发病率范围为 1999 年的 0.65 至 2006 年的 1.10，平均为 0.85，与欧洲国家相似。尽管在日本普通人群中，朊蛋白基因 129 密码子多态性的蛋氨酸纯合子（93%）非常常见，但与西方国家一样，日本散发性 Creutzfeldt-Jakob 病与 129 密码子纯合子显著相关（97.5%）。在散发性 Creutzfeldt-Jakob 病中，MM1 型（Parchi 分类）最为常见，与西方国家相同。在非典型散发性 Creutzfeldt-Jakob 病病例中，MM2 型最为常见，可能与日本人群中蛋氨酸等位基因的比例非常高有关。至于医源性 Creutzfeldt-Jakob 病，日本仅报告了硬脑膜移植相关性 Creutzfeldt-Jakob 病病例，结合之前监测系统的数据，硬脑膜移植相关性 Creutzfeldt-Jakob 病的总数为 138 例，占全世界硬脑膜移植相关性 Creutzfeldt-Jakob 病患者的大多数。关于遗传性朊病毒病，朊蛋白基因最常见的突变是 V180I（41.2%），其次是 P102L（18.1%）、E200K（17.1%）和 M232R（15.3%），这种分布与欧洲的情况有很大不同。特别是，V180I 和 M232R 是全世界罕见的突变。携带 V180I 或 M232R 突变的患者很少有朊病毒病家族史，这表明有必要对散发性病例进行基因检测，以将其与散发性 Creutzfeldt-Jakob 病区分开来。总之，我们前瞻性的 10 年监测显示，硬脑膜移植相关性 Creutzfeldt-Jakob 病频繁发生，与西方国家相比，日本散发性 Creutzfeldt-Jakob 病和遗传性朊病毒病的独特表型与朊病毒蛋白基因突变和多态性的特征分布有关。
