Zakład Genetyki, Instytut Psychiatrii i Neurologii w Warszawie, Al. Sobieskiego 9, Warszawa, Polska.
Neurol Neurochir Pol. 2012 Nov-Dec;46(6):509-18. doi: 10.5114/ninp.2012.32353.
The aim of the study was to perform molecular analysis in a group of patients affected with prion disease. Diagnosis was based on results of clinical and/or histopathological examination of the brain. This is the largest investigation of this type performed so far in Poland.
Analysed material contained 36 cases of prion disease, including 35 cases of Creutzfeldt-Jakob disease and one case of Gerstmann-Sträussler-Scheinker disease, as well as two familial cases initially suspected of Huntington disease and Alzheimer disease. The control group consisted of 87 subjects. The most frequent known mutations in the PRNP gene were looked for, namely those in codons 102, 117, 178, 200, 217 and OPRI; the polymorphism Met/Val in codon 129 was also analysed. The methods applied were PCR-RFLP and DNA sequencing.
The following mutations were found: E200K in 5 families, P102L in one family (previously identified), D178N in one family and 6OPRI in one family. Overall, mutations were detected in 17 persons (including 8 preclinical ones) from 8 pedigrees. Highly significant difference of codon 129 Met/Val heterozygosity frequencies was found between the affected subjects and the controls. Frequency of the familial form of prion disease in the material analysed was 14%.
Screening for mutations in the PRNP gene should be performed in all diagnosed cases of prion disease and in cases of familial occurrence of early onset dementia of unknown aetiology. Families with identified mutations should be offered genetic counselling and informed of risks of blood and organs' donation.
本研究的目的是对一组朊病毒病患者进行分子分析。诊断基于大脑临床和/或组织病理学检查的结果。这是迄今为止在波兰进行的此类最大规模的调查。
分析材料包含 36 例朊病毒病病例，包括 35 例克雅氏病和 1 例格斯特曼-施特劳斯勒-谢因克病病例，以及 2 例最初疑似亨廷顿病和阿尔茨海默病的家族病例。对照组由 87 名受试者组成。寻找最常见的 PRNP 基因突变，即密码子 102、117、178、200、217 和 OPRI 中的突变；还分析了密码子 129 中的 Met/Val 多态性。应用的方法是 PCR-RFLP 和 DNA 测序。
发现了以下突变：5 个家族中的 E200K、1 个家族中的 P102L（先前已鉴定）、1 个家族中的 D178N 和 1 个家族中的 6OPRI。总共在 8 个家族中的 17 人（包括 8 例临床前病例）中发现了突变。受影响的受试者与对照组之间的密码子 129 Met/Val 杂合度存在显著差异。分析材料中家族性朊病毒病的频率为 14%。
应在所有诊断为朊病毒病的病例以及病因不明的早发性家族性痴呆病例中进行 PRNP 基因突变筛查。应向发现突变的家族提供遗传咨询，并告知血液和器官捐赠的风险。
