Mead Simon, Joiner Susan, Desbruslais Melanie, Beck Jonathan A, O'Donoghue Michael, Lantos Peter, Wadsworth Jonathan D F, Collinge John
MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Arch Neurol. 2007 Dec;64(12):1780-4. doi: 10.1001/archneur.64.12.1780.
Variant Creutzfeldt-Jakob disease (vCJD) is an acquired prion disease causally related to bovine spongiform encephalopathy that has occurred predominantly in young adults. All clinical cases studied have been methionine homozygotes at codon 129 of the prion protein gene (PRNP) with distinctive neuropathological findings and molecular strain type (PrP(Sc) type 4). Modeling studies in transgenic mice suggest that other PRNP genotypes will also be susceptible to infection with bovine spongiform encephalopathy prions but may develop distinctive phenotypes.
To describe the histopathologic and molecular investigation in a young British woman with atypical sporadic CJD and valine homozygosity at PRNP codon 129.
Case report, autopsy, and molecular analysis.
Specialist neurology referral center, together with the laboratory services of the MRC [Medical Research Council] Prion Unit. Subject Single hospitalized patient.
Autopsy findings and molecular investigation results.
Autopsy findings were atypical of sporadic CJD, with marked gray and white matter degeneration and widespread prion protein (PrP) deposition. Lymphoreticular tissue was not available for analysis. Molecular analysis of PrP(Sc) (the scrapie isoform of PrP) from cerebellar tissue demonstrated a novel PrP(Sc) type similar to that seen in vCJD (PrP(Sc) type 4). However, this could be distinguished from the typical vCJD pattern by an altered protease cleavage site in the presence of the metal ion chelator EDTA.
Further studies will be required to characterize the prion strain seen in this patient and to investigate its etiologic relationship with bovine spongiform encephalopathy. This case illustrates the importance of molecular analysis of prion disease, including the use of EDTA to investigate the metal dependence of protease cleavage patterns of PrP(Sc).
变异型克雅氏病（vCJD）是一种与牛海绵状脑病有因果关系的后天性朊病毒病，主要发生在年轻人中。所有研究的临床病例在朊病毒蛋白基因（PRNP）第129密码子处均为甲硫氨酸纯合子，具有独特的神经病理学表现和分子毒株类型（PrP(Sc) 4型）。转基因小鼠的模型研究表明，其他PRNP基因型也易感染牛海绵状脑病朊病毒，但可能会出现独特的表型。
描述一名英国年轻女性患非典型散发性克雅氏病且PRNP第129密码子为缬氨酸纯合子的组织病理学和分子研究情况。
病例报告、尸检及分子分析。
专业神经科转诊中心，以及医学研究理事会朊病毒研究室（MRC）的实验室服务部门。研究对象为一名住院患者。
尸检结果和分子研究结果。
尸检结果不典型，表现为明显的灰质和白质变性以及广泛的朊病毒蛋白（PrP）沉积。无法获取淋巴网状组织进行分析。对小脑组织中PrP(Sc)（PrP的瘙痒病异构体）的分子分析显示出一种类似于vCJD所见的新型PrP(Sc)类型（PrP(Sc) 4型）。然而，在存在金属离子螯合剂乙二胺四乙酸（EDTA）的情况下，其蛋白酶切割位点发生改变，这可将其与典型的vCJD模式区分开来。
需要进一步研究来确定该患者中所见的朊病毒毒株特征，并调查其与牛海绵状脑病的病因关系。该病例说明了朊病毒病分子分析的重要性，包括使用EDTA来研究PrP(Sc)蛋白酶切割模式的金属依赖性。
