Kosorinova Dana, Belay Girma, Zakova Dana, Stelzer Martin, Mitrova Eva
Department of Prion Diseases, Faculty of Medicine, Slovak Medical University, 831 01 Bratislava, Slovakia.
Pathogens. 2021 Apr 6;10(4):435. doi: 10.3390/pathogens10040435.
The most frequent human prion disease is Creutzfeldt-Jakob disease (CJD). It occurs as sporadic (sCJD), genetic (gCJD), iatrogenic (iCJD) form and as variant CJD. The genetic form represents about 10-15% of confirmed cases worldwide, in Slovakia as much as 65-75%. Focal accumulation of gCJD was confirmed in Orava region. The most common point mutation of the prion protein gene ( is E200K. CJD has a long asymptomatic phase and it is not known when the carriers of the mutation E200K become infectious. Precautions to prevent iCJD are focused especially on clinical CJD cases, but asymptomatic CJD-specific mutation carriers cannot be excluded, and represent a potential genetic CJD-risk group. The aim of this study was to determine the occurrence, frequency and geographic distribution of the E200K mutation among the newborns, comparing the areas of focal accumulation of gCJD with extra-focal ones, as well as distribution of the polymorphism M129V of the gene. A total of 2915 samples of dry blood spots from anonymous newborns were analyzed. We used RealTime PCR method to determine the presence of the E200K mutation and the M129V polymorphism. Genetic testing revealed 13 carriers of the E200K mutation. Investigation of the M129V polymorphism affirmed higher representation of methionine homozygotes (48% MM, 44% MV, 8% VV). Achieved results fully confirmed our previous observations concerning both the specific and nonspecific genetic CJD risk among the Slovak general population. The 48% of methionine homozygotes and 4 carriers of the E200K mutation among 1000 live-born children in Slovakia underline the benefits of genetic testing.
最常见的人类朊病毒病是克雅氏病（CJD）。它以散发性（sCJD）、遗传性（gCJD）、医源性（iCJD）形式以及变异型CJD出现。遗传性形式在全球确诊病例中约占10 - 15%，在斯洛伐克高达65 - 75%。已证实奥拉瓦地区存在gCJD的局灶性聚集。朊病毒蛋白基因最常见的点突变是E200K。CJD有很长的无症状期，目前尚不清楚E200K突变携带者何时具有传染性。预防医源性CJD的措施尤其侧重于临床CJD病例，但不能排除无症状的CJD特异性突变携带者，他们是潜在的遗传性CJD风险群体。本研究的目的是确定新生儿中E200K突变的发生率、频率和地理分布，比较gCJD局灶性聚集区域与非局灶性区域，以及朊病毒蛋白基因多态性M129V的分布。共分析了2915份匿名新生儿干血斑样本。我们使用实时荧光定量PCR方法来确定E200K突变和M129V多态性的存在。基因检测发现了13名E200K突变携带者。对M129V多态性的研究证实甲硫氨酸纯合子的比例更高（48%为MM，44%为MV，8%为VV）。所取得的结果充分证实了我们之前关于斯洛伐克普通人群中特异性和非特异性遗传性CJD风险的观察结果。斯洛伐克每1000名活产儿童中有48%的甲硫氨酸纯合子和4名E200K突变携带者，这突出了基因检测的益处。
