Rodríguez-Martínez Ana B, López de Munain Adolfo, Ferrer Isidro, Zarranz Juan J, Atarés Begoña, Villagra Nuria T, Arteagoitia Jose M, Garrido Joseba M, Juste Ramón A
Department of Animal Health, Neiker-Tecnalia, Berreaga 1, Derio, Bizkaia, 48160, Spain.
J Med Case Rep. 2012 Oct 11;6:348. doi: 10.1186/1752-1947-6-348.
The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported.
A 74-year-old Caucasian woman showed a sporadic Creutzfeldt-Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77.Neuropathological findings showed: spongiform change in the patient's cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous.
Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt-Jakob disease. This highlights the importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies.
已有文献报道同一个体中存在不同分子类型的经典抗蛋白酶朊病毒蛋白，然而，据我们所知，尚未有同时发现这些蛋白与最近描述的蛋白酶敏感变体或可变蛋白酶敏感朊病毒病的相关报道。
一名74岁的白种女性表现出散发性克雅氏病的临床表型，伴有反应性抑郁，随后出现认知障碍、伴有假性延髓综合征的运动不能-强直型帕金森病以及伴有运动失用、视觉空间定向障碍和明显额叶功能障碍特征（如抓握、掌颏反射和口周反射亢进）的步态障碍。她于77岁时去世。神经病理学检查结果显示：患者大脑皮质、纹状体、丘脑和小脑分子层出现海绵状改变，皮质、丘脑和纹状体中有对蛋白酶K敏感的突触样、点状或靶样朊病毒蛋白沉积；相同区域存在抗蛋白酶K的朊病毒蛋白；小脑分子层中有细长的斑块样抗蛋白酶K的朊病毒蛋白。蛋白酶K消化后朊病毒蛋白的分子分析显示免疫印迹中信号强度降低、蛋白呈梯状模式，且与未消化材料相比，PrPSc信号减少了71%。她的小脑显示出主要对蛋白酶K有抗性的2A型朊病毒蛋白。密码子129处的多态性基因型为缬氨酸纯合子。
据我们所知，朊病毒蛋白的分子分型以及临床和神经病理学数据揭示了首例在同一患者中不同蛋白酶敏感朊病毒蛋白共存的病例，该病例罕见，不符合目前可能或疑似散发性克雅氏病的临床诊断标准。这凸显了对多个脑区进行分子分析对于正确诊断罕见和非典型朊病毒病的重要性。
