Collinge J, Palmer M S
Department of Biochemistry and Molecular Genetics, St Mary's Hospital Medical School, Imperial College, London, U.K.
Philos Trans R Soc Lond B Biol Sci. 1994 Mar 29;343(1306):371-8. doi: 10.1098/rstb.1994.0031.
Human prion diseases occur in inherited, sporadic and acquired forms. The inherited forms are associated with coding mutations in the prion protein gene and the identification of one of these pathogenic mutations allows definitive diagnosis and has resulted in a widening of the previously recognized phenotypic spectrum of these diseases. Study of acquired prion disease provides evidence for genetic susceptibility to development of disease following treatment with contaminated pituitary hormones. Sporadic prion disease occurs predominantly in individuals homozygous with respect to a common PrP polymorphism at residue 129. The identification of pathogenic PrP alleles and the role of the codon 129 PrP gene polymorphism in determining susceptibility to prion disease provides strong support for the idea that an abnormal isoform of PrP, PrPSc, is the principal constituent of the prion and that its propagation involves direct PrP-PrP interactions which occur most readily between identical PrP molecules.
人类朊病毒病以遗传、散发和获得性形式出现。遗传形式与朊病毒蛋白基因中的编码突变相关，识别其中一种致病突变可进行明确诊断，并导致这些疾病先前公认的表型谱范围扩大。对获得性朊病毒病的研究为使用受污染的垂体激素治疗后发生疾病的遗传易感性提供了证据。散发性朊病毒病主要发生在第129位残基处具有常见PrP多态性的纯合个体中。致病性PrP等位基因的识别以及密码子129 PrP基因多态性在决定对朊病毒病易感性中的作用，为以下观点提供了有力支持：即PrP的异常异构体PrPSc是朊病毒的主要成分，其传播涉及直接的PrP-PrP相互作用，这种相互作用在相同的PrP分子之间最容易发生。
