Department of Neurology, Ghent University Hospital, Ghent, Belgium.
Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium.
J Neurol. 2024 Jan;271(1):263-273. doi: 10.1007/s00415-023-11968-9. Epub 2023 Sep 9.
Inherited prion diseases caused by two- to twelve-octapeptide repeat insertions (OPRIs) in the prion protein gene (PRNP) show significant clinical heterogeneity. This study describes a family with two new cases with a 4-OPRI mutation and two asymptomatic mutation carriers. The pooled analysis summarizes all cases reported in the literature to date and describes the relation between survival, age of onset, number of OPRI and codon 129 polymorphism. MEDLINE and Google Scholar were queried from database inception up to December 31, 2022. Age of onset was compared per number of OPRI and per codon 129 polymorphism using the Kruskal-Wallis and Wilcoxon-Mann-Whitney tests, respectively. Disease duration was modeled non-parametrically by a Kaplan-Meier model and semi-parametrically by a Cox model. This study comprised 164 patients. Lower number of OPRI and presence of valine (cis-V) versus methionine (cis-M) on codon 129 were associated with an older age of onset (P < 0.001 and P = 0.025, respectively) and shorter disease duration (P < 0.001 and P = 0.003, respectively). Within patients with 5- or more OPRI codon cis-V remained significantly associated with a shorter disease duration. Codon 129 homozygosity versus heterozygosity was not significantly associated with age of onset or disease duration (P = 0.076 and P = 0.409, respectively). This study summarized the largest cohort of patients with two- to twelve-OPRI to date. Lower number of OPRI and codon 129 cis-V is associated with an older age of onset and shorter disease duration, while homozygosity or heterozygosity on codon 129 was not.
由朊病毒蛋白基因 (PRNP) 中的两到十二个八肽重复插入 (OPRI) 引起的遗传性朊病毒病表现出显著的临床异质性。本研究描述了一个家族的两个新病例，这些病例具有 4-OPRI 突变和两个无症状突变携带者。汇总分析总结了迄今为止文献中报告的所有病例，并描述了存活时间、发病年龄、OPRI 数量和密码子 129 多态性之间的关系。从数据库创建开始到 2022 年 12 月 31 日，在 MEDLINE 和 Google Scholar 上进行了查询。使用 Kruskal-Wallis 和 Wilcoxon-Mann-Whitney 检验分别按 OPRI 数量和密码子 129 多态性比较发病年龄。使用 Kaplan-Meier 模型和半参数 Cox 模型对疾病持续时间进行非参数和半参数建模。本研究共纳入 164 例患者。OPRI 数量较少和密码子 129 上存在缬氨酸（顺式-V）而非蛋氨酸（顺式-M）与发病年龄较大（P < 0.001 和 P = 0.025）和疾病持续时间较短（P < 0.001 和 P = 0.003）相关。在具有 5 个或更多 OPRI 密码子顺式-V 的患者中，疾病持续时间仍显著较短。密码子 129 纯合性与杂合性与发病年龄或疾病持续时间无显著相关性（P = 0.076 和 P = 0.409）。本研究总结了迄今为止最大的 2-12-OPRI 患者队列。OPRI 数量较少和密码子 129 顺式-V 与发病年龄较大和疾病持续时间较短相关，而密码子 129 的纯合性或杂合性则无关。
