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

导言：Nitrini等人之前的报告。描述了一例具有额颞部临床特征的痴呆症，该病与PrP基因183密码子突变相关。这表明在临床诊断为额颞叶痴呆(FTD)的患者中，Prion病可能被低估了。此外，据报道，在有阳性家族史的FTD病例中，约有1040%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Prion蛋白和tau蛋白。诊断是根据Lund和曼彻斯特小组的FTD标准进行的。采用聚合酶链式反应和限制性片段长度多态分析方法，对上述外周血基因组DNA中的PRNP基因突变和多态性进行分析。关于tau蛋白基因…更多的是，总共16个与FTD有关的突变已被报道。在这项研究中，我们收集了29个日本FTD人群的DNA样本。我们分析了29例日本FTD患者已报道的16个突变(1个突变(Gly272Val)(外显子9)，5(Asn279Lys，Del280，Leu284Leu，Pro301Leu和Ser305Asn)(外显子10)，2(Val337Met，Lys369Ile)(外显子12)，2(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)。结果：在32例FTD患者中未发现错义突变和插入突变。一名患者被发现在180密码子(Val到Ile)上有错义突变。我们在日本的FTD样本中没有发现MAPT基因突变的报道。结论：在33例日本FTD患者中，有1例被证实患有Pron病。我们的结果表明，对于有FTD临床特征的患者，应考虑Pron病。我们的结果还表明，MAPT基因可能不参与日本人FTD的病理生理机制。较少

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