Fatal familial insomnia with an unusual prion protein deposition pattern: an autopsy report with an experimental transmission study
Fatal familial insomnia with an unusual prion protein deposition pattern: an autopsy report with an experimental transmission study
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DOI：
10.1111/j.1365-2990.2004.00592.x
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发表时间：
2005-02-01
影响因子：
5
通讯作者：
Iwaki, T
中科院分区：
文献类型：
--
作者：
Sasaki, K;Doh-ura, K;Iwaki, T
我们最近进行了一个日本患者谁有朊病毒蛋白基因突变负责致命的家族性失眠症（FFI）的尸检。病人最初发展为小脑性共济失调，但最终在疾病晚期表现为失眠、运动过度性谵妄、自主神经体征和肌阵挛。组织学检查发现丘脑和下橄榄核有明显的神经元丢失;然而，朊病毒蛋白（PrP）沉积在这些病变的免疫组化未得到证实。相反，PrP沉积和海绵状变化都是显着的大脑皮质内，而特定的PrP沉积也观察到小脑皮质内。该病例大脑皮质中异常的蛋白酶抗性PrP（PrPres）分子显示PrPres 2型模式，与FFI病例一致，但传播研究表明，该病例中的病原体与经典FFI病例中的病原体不同。通过用大脑皮层制成的匀浆接种，将疾病传播给小鼠，并注意到与先前报道的神经病理学特征不同的神经病理学特征。这些发现表明，在这种情况下，一个离散的病原体参与疾病的可能性。我们认为，不仅PrP基因的基因型和其他一些未知的遗传因素，而且病原体菌株的变化可能是负责这种疾病的不同的临床和病理特征。
We recently performed a post-mortem examination on a Japanese patient who had a prion protein gene mutation responsible for fatal familial insomnia (FFI). The patient initially developed cerebellar ataxia, but finally demonstrated insomnia, hyperkinetic delirium, autonomic signs and myoclonus in the late stage of the illness. Histological examination revealed marked neuronal loss in the thalamus and inferior olivary nucleus; however, prion protein (PrP) deposition was not proved in these lesions by immunohistochemistry. Instead, PrP deposition and spongiform change were both conspicuous within the cerebral cortex, whereas particular PrP deposition was also observed within the cerebellar cortex. The abnormal protease-resistant PrP (PrPres) molecules in the cerebral cortex of this case revealed PrPres type 2 pattern and were compatible with those of FFI cases, but the transmission study demonstrated that a pathogen in this case was different from that in a case with classical FFI. By inoculation with homogenate made from the cerebral cortex, the disease was transmitted to mice, and neuropathological features that were distinguishable from those previously reported were noted. These findings indicate the possibility that a discrete pathogen was involved in the disease in this case. We suggest that not only the genotype of the PrP gene and some other as yet unknown genetic factors, but also the variation in pathogen strains might be responsible for the varying clinical and pathological features of this disease.