Prion protein and tau protein gene analysis in frontotemporal dementia in Japan

日本额颞叶痴呆的朊病毒蛋白和tau蛋白基因分析

• 批准号: 11670948
• 负责人: OGOMORI Koji
• 金额: $ 1.66万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670948/
• 关键词: dementia; prion protein; tau protein; frontotemporal dementia; Pick's disease; MAPT; タウ遺伝子; 分子生物学

Introduction : Previous report by Nitrini, et al. described a dementia with frontotemporal clinical features associated with a prion protein gene mutation at codon 183. This suggests that prion disease might be underestimated in the patients clinically diagnosed as frontotemporal dementia(FTD). In addition, It is reported that approximately 10 40% of FTD cases with a positive family history are caused by mutations in the microtubule-associated protein tau (MAPT) gene. Therefore, we examined prion protein and tau protein in the Japanese patients with FTD.Subjects and methods : We analyzed the prion protein gene(PRNP) in 33 patients with FTD. The diagnosis was made clinically according to the Lund and Manchester Groups criteria for FTD. All of the PRNP mutations and polymorphisms described previously were analyzed in the genomic DNA extracted from the peripheral blood cells, by using polymerase chain reaction and restriction fragment length polymorphism method. Concerning tau protein gen … More e, total 16 mutations which are responsible for FTD have been reported. In this study, we have collected DNA samples from 29 FTD in Japanese population. We have analyzed 16 reported mutations (1 mutation (Gly272Val)(exon 9), 5 (Asn279Lys, Del280, Leu284Leu, Pro301Leu and Ser305Asn)(exon10), 2 (Val337Met, Lys369Ile)(exon12), 2 (Gly389Arg and Arg406Trp) (exon13/14), and 6 stem-loop mutations (+1G/A, +3G/A,+12+13A/G, +14C/T, +16C/T, (intron 10)) of human MAPT gene in Japanese FTD patients (n=29). Direct sequencing method by capillary electrophoresis was employed for this analysis.Results : We found none of the missense mutations or insertional mutations in 32 patients with FTD. One patient was found to have a missense mutation at codon 180(Val to Ile). We found no reported MAPT gene mutations in the Japanese FTD samples.Conclusion : One patient was proved to have prion disease among 33 Japanese patients with FTD. Our results indicate that prion disease should be considered in the patients with clinical features of FTD. Our results also suggest that MAPT gene may not be involved in the pathophysiological mechanisms of FTD in Japanese population. Less

简介：Nitrini等人先前的报道描述了一种与密码子183处朊蛋白基因突变相关的额颞叶痴呆临床特征。这表明在临床诊断为额颞叶痴呆（FTD）的患者中，朊病毒疾病可能被低估了。此外，据报道，有阳性家族史的FTD病例中约有10.40%是由微管相关蛋白tau （MAPT）基因突变引起的。因此，我们检测了日本FTD患者的朊病毒蛋白和tau蛋白。研究对象和方法：对33例FTD患者的朊蛋白基因（PRNP）进行分析。临床诊断根据隆德和曼彻斯特组的FTD标准。利用聚合酶链反应和限制性片段长度多态性方法，在提取的外周血细胞基因组DNA中分析了前面描述的所有PRNP突变和多态性。在tau蛋白基因方面，共有16个突变被报道导致FTD。在这项研究中，我们收集了29名日本人的FTD DNA样本。我们分析了日本FTD患者中已报道的16个突变(1个突变（Gly272Val）（外显子9），5个突变（Asn279Lys, Del280, Leu284Leu， Pro301Leu和Ser305Asn）（外显子10），2个突变（Val337Met, Lys369Ile）（外显子12），2个突变（Gly389Arg和Arg406Trp）（外显子13/14），以及6个茎环突变（+1G/A, +3G/A,+12+13A/G, +14C/T, +16C/T,（内含子10））。采用毛细管电泳直接测序法进行分析。结果：32例FTD患者中未发现错义突变或插入突变。1例患者发现密码子180（Val到Ile）有错义突变。我们在日本FTD样本中没有发现MAPT基因突变的报道。结论：33例日本FTD患者中有1例被证实为朊病毒病。我们的结果提示，在有FTD临床特征的患者中应考虑朊病毒疾病。我们的结果也提示MAPT基因可能不参与日本人群FTD的病理生理机制。少