Department of Bionano Technology, Gachon University, Seongnam 13120, Republic of Korea.
Department of Industrial and Environmental Engineering, Graduate School of Environment, Gachon University, Seongnam 13120, Republic of Korea.
Int J Mol Sci. 2022 Dec 30;24(1):625. doi: 10.3390/ijms24010625.
Prion gene (PRNP) mutations are associated with diverse disease phenotypes, including familiar Creutzfeldt-Jakob Disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), and fatal familial insomnia (FFI). Interestingly, PRNP mutations have been reported in patients diagnosed with Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease, and frontotemporal dementia. In this review, we describe prion mutations in Asian countries, including Republic of Republic of Korea, China, and Japan. Clinical phenotypes and imaging data related to these mutations have also been introduced in detail. Several prion mutations are specific to Asians and have rarely been reported in countries outside Asia. For example, PRNP V180I and M232R, which are rare in other countries, are frequently detected in Republic of Korea and Japan. PRNP T188K is common in China, and E200K is significantly more common among Libyan Jews in Israel. The A117V mutation has not been detected in any Asian population, although it is commonly reported among European GSS patients. In addition, V210I or octapeptide insertion is common among European CJD patients, but relatively rare among Asian patients. The reason for these differences may be geographical or ethical isolation. In terms of clinical phenotypes, V180I, P102L, and E200K present diverse clinical symptoms with disease duration, which could be due to other genetic and environmental influences. For example, rs189305274 in the ACO1 gene may be associated with neuroprotective effects in cases of V180I mutation, leading to longer disease survival. Additional neuroprotective variants may be possible in cases featuring the E200K mutation, such as KLKB1, KARS, NRXN2, LAMA3, or CYP4X1. E219K has been suggested to modify the disease course in cases featuring the P102L mutation, as it may result in the absence of prion protein-positive plaques in tissue stained with Congo red. However, these studies analyzed only a few patients and may be too preliminary. The findings need to be verified in studies with larger sample sizes or in other populations. It would be interesting to probe additional genetic factors that cause disease progression or act as neuroprotective factors. Further studies are needed on genetic modifiers working with prions and alterations from mutations.
朊病毒基因 (PRNP) 突变与多种疾病表型相关,包括家族性克雅氏病 (CJD)、格斯特曼-施特劳斯勒-谢因克病 (GSS) 和致命性家族性失眠症 (FFI)。有趣的是,PRNP 突变也在被诊断患有阿尔茨海默病、路易体痴呆、帕金森病和额颞叶痴呆的患者中被报道。在这篇综述中,我们描述了亚洲国家(包括韩国、中国和日本)的朊病毒突变。还详细介绍了与这些突变相关的临床表型和影像学数据。一些朊病毒突变是亚洲特有的,在亚洲以外的国家很少被报道。例如,在其他国家很少见的 PRNP V180I 和 M232R 在韩国和日本则频繁被检测到。PRNP T188K 在我国常见,E200K 在以色列的利比亚犹太人中显著更为常见。A117V 突变尚未在任何亚洲人群中检测到,尽管它在欧洲 GSS 患者中经常报道。此外,V210I 或八肽插入在欧洲 CJD 患者中常见,但在亚洲患者中相对罕见。这些差异的原因可能是地理位置或伦理隔离。在临床表型方面,V180I、P102L 和 E200K 具有不同的临床表现和疾病持续时间,这可能是由于其他遗传和环境因素的影响。例如,ACO1 基因中的 rs189305274 可能与 V180I 突变病例中的神经保护作用有关,导致疾病生存时间延长。在 E200K 突变病例中,可能存在其他神经保护变异,如 KLKB1、KARS、NRXN2、LAMA3 或 CYP4X1。E219K 被认为可以改变 P102L 突变病例的疾病进程,因为它可能导致刚果红染色的组织中没有朊病毒蛋白阳性斑块。然而,这些研究仅分析了少数患者,可能还为时过早。这些发现需要在更大样本量的研究或其他人群中进行验证。研究其他导致疾病进展或作为神经保护因素的遗传因素会很有趣。需要进一步研究与朊病毒一起作用的遗传修饰因子以及突变引起的改变。