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

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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