title: Molecular genetics of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17).
abstract: Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is characterised by behavioural, cognitive and motor disturbances. Pathological changes in the brain include fronto-temporal atrophy with neuronal loss, grey white matter gliosis and superficial cortical spongiform. In addition, intraneuronal tau inclusions with the variable occurrence of glial inclusions are present in FTDP-17 brains. The pattern of inheritance in FTDP-17 is autosomal dominant with an early age of onset (45-65 years). The identification of mutations in the tau gene in FTDP-17 demonstrated that there is a direct link between tau dysfunction and neurodegeneration. To date, 14 missense mutations, a three base pair deletion (deltaK280) and seven splice site mutations have been found in over 50 FTDP-17 families from different ethnic groups. All of the known mutations occur in the C-terminal end of tau, with the majority affecting exons 9-12, which encode the microtubule-binding repeats. The mutations have multiple effects on the biology and function of tau. These varied pathogenic mechanisms most likely explain the wide range of clinical and neuropathological features observed in different families with FTDP-17.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland. annkowal@rose.man.poznan.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Kowalska
mesh_terms: D002886:Chromosomes, Human, Pair 17; D003704:Dementia / Q000145:classification / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D008869:Microtubule-Associated Proteins; D009154:Mutation; D020734:Parkinsonian Disorders / Q000235:genetics*; D010766:Phosphorylation; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D016875:tau Proteins