Novel G335V mutation in the tau gene associated with early onset familial frontotemporal dementia.
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.
Neumann
Manuela
M
Center for Neuropathology and Prion Research, Ludwig Maximilians University, Munich, Germany.
Diekmann
Silvia
S
Bertsch
Uwe
U
Vanmassenhove
Ben
B
Bogerts
Bernhard
B
Kretzschmar
Hans A
HA
D017668:Age of Onset; D000925:Anticoagulants; D003704:Dementia / Q000235:genetics*; D005192:Family Health; D005260:Female; D005858:Germany; D006493:Heparin; D006801:Humans; D008297:Male; D008870:Microtubules / Q000378:metabolism; D020125:Mutation, Missense; D010375:Pedigree; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
D000925:Anticoagulants; D011994:Recombinant Proteins; D016875:tau Proteins; D006493:Heparin