Neumann Manuela, Diekmann Silvia, Bertsch Uwe, Vanmassenhove Ben, Bogerts Bernhard, Kretzschmar Hans A
Center for Neuropathology and Prion Research, Ludwig Maximilians University, Munich, Germany.
Neurogenetics. 2005 May;6(2):91-5. doi: 10.1007/s10048-005-0210-y. Epub 2005 Mar 12.
Mutations in the tau gene cause familial frontotemporal dementia and parkinsonism linked to chromosome 17. Here we describe a novel missense mutation in exon 12 of the tau gene, G335V, in a German family with frontotemporal dementia of early age at onset, in the third decade of life. Functional analysis of recombinant tau protein with the G335V mutation showed a dramatically reduced ability to promote microtubule assembly and a more rapid and accelerated tau filament formation, suggesting that the primary effect of the mutation might be the provision of a pool of unbound tau making it available for aberrant tau aggregation.
tau基因的突变会导致与17号染色体相关的家族性额颞叶痴呆和帕金森综合征。在此，我们描述了一个德国家族中tau基因外显子12的一种新型错义突变G335V，该家族患有早发型额颞叶痴呆，发病年龄在生命的第三个十年。对具有G335V突变的重组tau蛋白进行功能分析表明，其促进微管组装的能力显著降低，且tau丝形成更快、更迅速，这表明该突变的主要影响可能是提供了一批未结合的tau，使其易于发生异常的tau聚集。
