Frontzek Karl, Moos Rita, Schaper Elke, Jann Lukas, Herfs Gregor, Zimmermann Dieter R, Aguzzi Adriano, Budka Herbert
a Institute of Neuropathology; University Hospital of Zurich ; Zurich , Switzerland;
b Vital-IT group; SIB Swiss Institute of Bioinformatics ; Lausanne , Switzerland;
Prion. 2015;9(6):444-8. doi: 10.1080/19336896.2015.1121356.
Human genetic prion diseases have invariably been linked to alterations of the prion protein (PrP) gene PRNP. Two sisters died from probable Creutzfeldt-Jakob disease (CJD) in Switzerland within 14 y. At autopsy, both patients had typical spongiform change in their brains accompanied by punctuate deposits of PrP. Biochemical analyses demonstrated proteinase K-resistant PrP. Sequencing of PRNP showed 2 wild-type alleles in both siblings. Retrospectively, clinical data revealed a history of dural transplantation in the initially deceased sister, compatible with a diagnosis of iatrogenic CJD. Clinical and familial histories provided no evidence for potential horizontal transmission. This observation of 2 siblings suffering from CJD without mutations in the PRNP gene suggests potential involvement of non-PRNP genes in prion disease etiology.
人类遗传性朊病毒疾病一直与朊病毒蛋白（PrP）基因PRNP的改变有关。在瑞士，两姐妹在14年内死于可能的克雅氏病（CJD）。尸检时，两名患者的大脑均有典型的海绵状改变，并伴有PrP的点状沉积。生化分析显示存在蛋白酶K抗性PrP。PRNP测序显示两名兄弟姐妹均有2个野生型等位基因。回顾性分析临床数据发现，最初去世的姐姐有硬脑膜移植史，符合医源性CJD的诊断。临床和家族史均未提供潜在水平传播的证据。这两名患有CJD但PRNP基因无突变的兄弟姐妹的病例表明，非PRNP基因可能参与了朊病毒疾病的病因。
