Genetic PrP Prion Diseases
Genetic PrP Prion Diseases
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DOI：
10.1101/cshperspect.a033134
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发表时间：
2018-05-01
影响因子：
7.2
通讯作者：
Geschwind, Michael D.
中科院分区：
文献类型：
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作者：
Kim, Mee-Ohk;Takada, Leonel T.;Geschwind, Michael D.
由朊蛋白基因（PRNF）突变引起的遗传性朊病毒病（gPrD）已被分类为遗传性克雅氏病（Creutzfeldt-Jakob disease）、Gerstmann-Straussler-Scheinker disease或致死性家族性失眠症。PRNP中的突变可以是错义、无义和/或八肽重复插入或可能缺失。这些突变可以产生不同的临床特征。它们也可能显示不同的辅助测试结果和神经病理学结果。虽然大多数gPrD具有快速进展，存活时间短至几个月，但许多也表现为共济失调或帕金森病，其在几年至几年内下降较慢。一些非常罕见的突变表现为神经精神疾病，具有包括胃肠道疾病和神经病在内的全身症状;这些形式可以持续数年至数十年。在这篇综述中，我们根据gPrDs的典型进展速度和持续时间将其分为快速、缓慢或混合类型，并回顾了这些疾病表现出的广泛表型。
Genetic prion diseases (gPrDs) caused by mutations in the prion protein gene (PRNF, have been classified as genetic Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker disease, or fatal familial insomnia. Mutations in PRNP can be missense, nonsense, and/or octapeptide repeat insertions or, possibly, deletions. These mutations can produce diverse clinical features. They may also show varying ancillary testing results and neuropathological findings. Although the majority of gPrDs have a rapid progression with a short survival time of a few months, many also present as ataxic or parkinsonian disorders, which have a slower decline over a few to several years. A few very rare mutations manifest as neuropsychiatric disorders, with systemic symptoms that include gastrointestinal disorders and neuropathy; these forms can progress over years to decades. In this review, we classify gPrDs as rapid, slow, or mixed types based on their typical rate of progression and duration, and we review the broad spectrum of phenotypes manifested by these diseases.