title: Missense and splice site mutations in tau associated with FTDP-17: multiple pathogenic mechanisms.
abstract: Recent identification of mutations in the gene encoding the microtubule-associated protein tau in the inherited frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) has demonstrated that tau dysfunction can lead to neurodegeneration. At least nine missense mutations and one deletion mutation (DeltaK280) have been identified in exons 9 through 13 that encode the microtubule-binding domains of tau. In addition, five mutations have been found close to the 5' splice site of exon 10. The FTDP-17 missense and splice site mutations have multiple effects on the biology and function of tau. It is likely that these varied pathogenic mechanisms explain the wide range of clinical and neuropathologic features observed in the FTDP-17 tauopathies.
authors.affiliation: Mayo Clinic Jacksonville, Jacksonville, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hutton
mesh_terms: D005091:Exons / Q000235:genetics*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D022821:RNA Splice Sites; D016875:tau Proteins