Journal of Applied Genetics 43(4), 2002, pp. 535-543

A novel mutation at position +11 in the intron following exon 10 of the tau gene in FTDP-17

Anna KOWALSKA, Masato HASEGAWA, Katsuichi MIYAMOTO, Ichiro AKIGUCHI, Akito IKEMOTO, Keikichi TAKAHASHI, Wataru ARAKI, Takeshi TABIRA

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.

Key words: alternative splicing, exon-trapping analysis, frontotemporal dementia, FTDP-17, microtubule-associated tau protein, mutation, tau gene.

Correspondence: A. KOWALSKA, Institute of Human Genetics, Polish Academy of Sciences, ul. Strzeszynska 32, 60-479 Poznan, Poland, e-mail: annkowal@rose.man.poznan.pl