Genetic Creutzfeldt-Jakob disease‐M232R with the cooccurrence of multiple prion strains, M1+ M2C + M2T: Report of an autopsy case
Genetic Creutzfeldt-Jakob disease‐M232R with the cooccurrence of multiple prion strains, M1+ M2C + M2T: Report of an autopsy case
复制标题
遗传性克雅氏病-M232R与多种朊病毒株共存，M1+M2C+M2T：尸检病例报告
DOI：
10.1111/neup.12722
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发表时间：
2021
期刊：
影响因子：
2.3
通讯作者：
Kitamoto Tetsuyuki
中科院分区：
文献类型：
--
作者：
Shintaku Masayuki;Nakamura Takeshi;Kaneda Daita;Shinde Akiyo;Kusaka Hirofumi;Takeuchi Atsuko;Kitamoto Tetsuyuki
遗传性克雅氏病（gCJD）在朊病毒蛋白基因（gCJD-M232 R）的密码子232处甲硫氨酸被精氨酸取代是罕见的，仅在日本报道。我们报告了一例gCJD-M232 R尸检病例，显示密码子129的等位基因为蛋氨酸纯合型，并存在多株蛋白酶抗性、朊蛋白异常亚型（PrPSc）M1 + M2 C + M2 T。该患者是一名54岁的日本男性，在21个月的临床病程后死亡，其特征为缓慢进行性痴呆和睡眠障碍。尸检时，大脑新皮质的神经纤维显示出广泛而严重的海绵状变化。葡萄状大融合空泡簇与细空泡混合。神经元损失为中度，但反应性星形胶质细胞增生为轻度。丘脑背内侧核和下橄榄核分别出现中度和重度神经元丢失。小脑分子层可见大量淀粉样斑块。PrPSc在大脑中的沉积模式主要为突触型，与小脑中的斑块相对应。还观察到液泡周围沉积。蛋白质印迹分析显示PrPScreen 2型占优势。此外，通过采用蛋白质印迹分析结合蛋白质错误折叠循环扩增（PMCA）方法，选择性地扩增次要的M2 T朊病毒株，我们证明了M2 T的存在，除了M1和M2 C株，在病人的大脑。PMCA是证明M2 T菌株存在的一种强有力的方法，尽管数量通常很小，传播也很困难。
Genetic Creutzfeldt‐Jakob disease (gCJD) with a methionine to arginine substitution at codon 232 of the prion protein gene (gCJD‐M232R) is rare and has only been reported in Japan. We report an autopsy case of gCJD‐M232R showing alleles of codon 129 that were homozygous for methionine and the presence of multiple strains of the protease‐resistant, abnormal isoform of prion protein (PrPSc), M1 + M2C + M2T. The patient, a 54‐year‐old Japanese man, died after a clinical course of 21 months characterized by slowly progressive dementia and sleep disturbance. At autopsy, the neuropil of the cerebral neocortex showed a widespread and severe spongiform change. Grape‐like clusters of large confluent vacuoles were admixed with fine vacuoles. Neuronal loss was moderate, but reactive astrocytosis was mild. The dorsomedial nucleus of the thalamus and the inferior olivary nucleus showed moderate and severe neuronal loss, respectively. Many amyloid plaques were present in the cerebellar molecular layer. PrPScdeposition pattern was predominantly the synaptic type in the cerebrum and corresponded to the plaques in the cerebellum. Perivacuolar deposition was also seen. Western blot analysis of PrPScrevealed the predominance of type 2. Moreover, by employing Western blot analysis in combination with the protein misfolding cyclic amplification (PMCA) method, which selectively amplifies the minor M2T prion strain, we demonstrated the presence of M2T, in addition to M1 and M2C strains, in the brain of the patient. PMCA was a powerful method for demonstrating the presence of the M2T strain, although the amount is often small and the transmission is difficult.