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Abstract：
Sporadic Creutzfeldt-Jakob disease (CJD) is a major human prion disease worldwide. CJD is a fatal neurodegenerative disease caused by an abnormal prion protein (PrPSc). To date, the exact etiology of sporadic CJD has not been fully elucidated. We investigated the E200K and V203I somatic mutations of the prion protein gene (PRNP) in sporadic CJD patients and matched healthy controls using pyrosequencing. In addition, we estimated the impact of somatic mutations on the human prion protein (PrP) using PolyPhen-2, PANTHER and PROVEAN. Furthermore, we evaluated the 3D structure and electrostatic potential of the human PrP according to somatic mutations using DeepView. The rates of PRNP K200 somatic mutation were significantly increased in the frontal cortex and hippocampus of sporadic CJD patients compared to the matched controls. In addition, the electrostatic potential of the human PrP was significantly changed by the K200 somatic mutation of the PRNP gene. To the best of our knowledge, this is the first report on an association of the PRNP K200 somatic mutation with sporadic CJD.
摘要：
散发性克雅氏病(CJD)是世界范围内一种主要的人类朊病毒病。CJD是一种由异常的朊病毒蛋白(PrPSc)引起的致命性神经退行性疾病。迄今为止,散发性CJD的确切病因尚未完全阐明。我们使用焦磷酸测序研究了散发性CJD患者和匹配的健康对照者中朊病毒蛋白基因（PRNP）的E200K和V203I体细胞突变。此外,我们使用PolyPhen-2,PANTHER和PROVEAN估计了体细胞突变对人朊病毒蛋白(PrP)的影响.此外，我们使用DeepView根据体细胞突变评估了人类PrP的3D结构和静电势。与匹配的对照组相比，散发性CJD患者的额叶皮质和海马中的PRNPK200体细胞突变率显着增加。此外,PRNP基因的K200体细胞突变显著改变了人PrP的静电势。据我们所知,这是关于PRNPK200体细胞突变与散发性CJD关联的第一份报告.
