title: A novel mutation at position +11 in the intron following exon 10 of the tau gene in FTDP-17.
abstract: Mutations in the microtubule-associated tau gene are responsible for frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). A reduced ability of the mutated microtubule-associated tau protein to interact with microtubules causes microtubule destabilization leading to deleterious effects on axonal transport and the formation of tau filaments. Here, we describe a new mutation of the tau gene, a T --> C transition at position +11 of the intron following exon 10 (T --> C 3'E10 +11) in the family showing frontotemporal dementia with very early age of onset (the first decade of proband's life). The T -->C 3'E10 +11 mutation caused a large increase in the proportion of transcripts containing exon 10 detected by exon-trapping analysis. Our study confirmed that the T --> C 3'E10 +11 mutation, as the other 5' splice site mutations of tau exon 10, modifies alternative splicing of exon 10.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, ul. Strzeszyńska 32, 60-479 Poznań, Poland. annkowal@rose.man.poznan.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Kowalska
authors.forename: Masato
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Katsuichi
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Akiguchi
authors.forename: Akito
authors.initials: A
authors.lastname: Ikemoto
authors.forename: Keikichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Wataru
authors.initials: W
authors.lastname: Araki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tabira
mesh_terms: D000818:Animals; D019556:COS Cells; D003704:Dementia / Q000235:genetics; D006801:Humans; D007438:Introns; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D016875:tau Proteins