title: Frequency of tau mutations in familial and sporadic frontotemporal dementia and other tauopathies.
abstract: Tau gene mutations with insoluble Tau neuropathology have been identified in pedigrees with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Other neurodegenerative diseases, including progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are also characterised by insoluble Tau neuropathology. This study sought to determine the nature and frequency of tau gene mutations in an affected proband cohort of patients within this spectrum of neurodegenerative diseases. Sixty-four individuals with clinical features consistent with FTD and other tauopathies were referred over a three year period. There was neuropathological confirmation of disease in 30%. Individuals were screened for mutations in the coding region and flanking intronic regions of the tau gene by direct sequencing of PCR products. Four confirmed tau gene mutations were identified representing 6.3 % for the total affected proband cohort. Tau gene mutations were found in three of twelve (25%) of the cases with a family history of dominantly inherited frontotemporal dementia, but in only one of 25 cases without a family history (4 %). Although tauopathies have been considered to result from genetic defects, screening for tau gene mutations in sporadic cases is not likely to identify pathogenic mutations.
authors.affiliation: Garvan Institute for Medical Research, 384 Victoria Street, Sydney, 2010, Australia.
authors.forename: Prudence M
authors.initials: PM
authors.lastname: Stanford
authors.forename: William S
authors.initials: WS
authors.lastname: Brooks
authors.forename: Erdahl T
authors.initials: ET
authors.lastname: Teber
authors.forename: Marianne
authors.initials: M
authors.lastname: Hallupp
authors.forename: Catriona
authors.initials: C
authors.lastname: McLean
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.forename: John B J
authors.initials: JB
authors.lastname: Kwok
authors.forename: Peter R
authors.initials: PR
authors.lastname: Schofield
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology; D015331:Cohort Studies; D003704:Dementia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D024801:Tauopathies / Q000235:genetics* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016875:tau Proteins