V180I遗传性克雅氏病:尸检患者下橄榄核严重变性,鉴定出M2T朊病毒株。

IF 1.3 4区 医学 Q4 CLINICAL NEUROLOGY
Neuropathology Pub Date : 2023-12-01 Epub Date: 2023-05-10 DOI:10.1111/neup.12908
Midori Watanabe, Kosei Nakamura, Rie Saito, Atsuko Takeuchi, Tetsuya Takahashi, Tetsuyuki Kitamoto, Osamu Onodera, Akiyoshi Kakita
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引用次数: 0

摘要

遗传性克雅氏病(gCJD)伴V180I突变(V180I gCJD)是日本最常见的gCJD类型,其特点是发病年龄较大,进展较慢,中度至重度皮质变性伴海绵状改变,脑干和小脑保留。下榄核(IO)变性在CJD患者中很少观察到,但已知发生在致命性家族性失眠症(FFI)和mm2 -地中海型散发性CJD (sCJD-MM2T)中,涉及2型朊病毒蛋白(M2T朊病毒)。在此,我们报告了一位81岁的日本女性,她最初出现抑郁症状,随后出现进行性认知障碍、肌阵挛和幻觉,并在临床病程23个月后死亡。失眠不明显。朊病毒蛋白(PrP)的遗传分析发现V180I突变在密码子129处具有蛋氨酸/缬氨酸杂合性。病理分析显示广泛的海绵状变性,皮层神经元丢失和弱突触型PrP沉积。除IO变性外,临床病理特征及Western blotting PrP条带图与文献报道的V180I型gCJD一致。定量分析显示,与sCJD-MM2T患者相比,脊髓IO的神经元密度明显降低,特别是在背侧区域,但与其他V180I gCJD和sCJD-MM1患者相比,神经元密度有所降低(该患者,2.3±0.53/mm2;1例sCJD-MM2T, 4.2±2;1例V180I型gCJD, 60.5±9.3;1例sCJD-MM1(84.5±17.9)。利用蛋白错误折叠循环扩增(PMCA)方法证实了M2T朊病毒株的存在,提示后者可能与V180I型gCJD的IO变性有关。解剖研究对于更好地了解CJD的本质是必要的,因为即使患者表现出共同的临床症状,病理分析也可能提供新的见解,就像这里的情况一样。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
V180I genetic Creutzfeldt-Jakob disease: Severe degeneration of the inferior olivary nucleus in an autopsied patient with identification of the M2T prion strain.

Genetic Creutzfeldt-Jakob disease (gCJD) with a V180I mutation (V180I gCJD) is the most common type of gCJD in Japan, characterized by an older age at onset, slower progression, and moderate to severe cortical degeneration with spongiform changes and sparing of the brainstem and cerebellum. Degeneration of the inferior olivary nucleus (IO) is rarely observed in patients with CJD but is known to occur in fatal familial insomnia (FFI) and MM2-thalamic-type sporadic CJD (sCJD-MM2T) involving type 2 prion protein (M2T prion). Here we report on an 81-year-old Japanese woman who initially developed depressive symptoms followed by progressive cognitive impairment, myoclonus, and hallucinations and died after a clinical course of 23 months. Insomnia was not evident. Genetic analysis of the prion protein (PrP) identified a V180I mutation with methionine/valine heterozygosity at codon 129. Pathologic analysis demonstrated extensive spongiform degeneration, neuronal loss in the cortices, and weak synaptic-type PrP deposition. Except for IO degeneration, the clinicopathologic features and Western blotting PrP band pattern were compatible with those of previously reported V180I gCJD cases. Quantitative analysis revealed that the neuronal density of the IO, especially in the dorsal area, was considerably reduced to the same extent as that of a patient with sCJD-MM2T but preserved in other patients with V180I gCJD and sCJD-MM1 (this patient, 2.3 ± 0.53/mm2 ; a patient with sCJD-MM2T, 4.2 ± 2; a patient with V180I gCJD, 60.5 ± 9.3; and a patient with sCJD-MM1, 84.5 ± 17.9). Use of the protein misfolding cyclic amplification (PMCA) method confirmed the presence of the M2T prion strain, suggesting that the latter might be associated with IO degeneration in V180I gCJD. Autopsy studies are necessary to better understand the nature of CJD, since even if patients present with the common clinical picture, pathologic analysis might provide new insights, as was the case here.

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来源期刊
Neuropathology
Neuropathology 医学-病理学
CiteScore
4.10
自引率
4.30%
发文量
105
审稿时长
6-12 weeks
期刊介绍: Neuropathology is an international journal sponsored by the Japanese Society of Neuropathology and publishes peer-reviewed original papers dealing with all aspects of human and experimental neuropathology and related fields of research. The Journal aims to promote the international exchange of results and encourages authors from all countries to submit papers in the following categories: Original Articles, Case Reports, Short Communications, Occasional Reviews, Editorials and Letters to the Editor. All articles are peer-reviewed by at least two researchers expert in the field of the submitted paper.
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