Center for Comprehensive Care and Research on Memory Disorders, Department of Neurology, University of Chicago, Chicago, IL 60637, USA.
J Geriatr Psychiatry Neurol. 2010 Dec;23(4):277-98. doi: 10.1177/0891988710383576. Epub 2010 Oct 11.
The prion diseases are a family of rare neurodegenerative disorders that result from the accumulation of a misfolded isoform of the prion protein (PrP), a normal constituent of the neuronal membrane. Five subtypes constitute the known human prion diseases; kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), fatal insomnia (FI), and variant CJD (vCJD). These subtypes are distinguished, in part, by their clinical phenotype, but primarily by their associated brain histopathology. Evidence suggests these phenotypes are defined by differences in the pathogenic conformation of misfolded PrP. Although the vast majority of cases are sporadic, 10% to 15% result from an autosomal dominant mutation of the PrP gene (PRNP). General phenotype-genotype correlations can be made for the major subtypes of CJD, GSS, and FI. This paper will review some of the general background related to prion biology and detail the clinical and pathologic features of the major prion diseases, with a particular focus on the genetic aspects that result in prion disease or modification of its risk or phenotype.
朊病毒病是一组罕见的神经退行性疾病，由朊病毒蛋白（PrP）的错误折叠异构体的积累引起，PrP 是神经元膜的正常组成部分。已知的人类朊病毒病有五种亚型；库鲁病、克雅氏病（CJD）、格斯特曼-施特劳斯勒-舍林氏症（GSS）、致死性失眠症（FI）和变异型克雅氏病（vCJD）。这些亚型部分通过其临床表型来区分，但主要通过其相关的脑组织病理学来区分。有证据表明，这些表型是由错误折叠 PrP 的致病性构象差异定义的。尽管绝大多数病例是散发性的，但 10%至 15%是由 PrP 基因（PRNP）的常染色体显性突变引起的。CJD、GSS 和 FI 的主要亚型可以进行一般表型-基因型相关性分析。本文将回顾一些与朊病毒生物学相关的一般背景，并详细描述主要朊病毒病的临床和病理特征，特别关注导致朊病毒病或改变其风险或表型的遗传方面。
