TY - JOUR
AU - Schellenberg, GD
AB - We investigated three separate families (designated D, F and G) with frontotemporal dementia that have the same molecular mutation in exon 10 of the tau gene ( P301L ). The families share many clinical characteristics, including behavioural aberrations, defective executive functions, language deficits, relatively preserved constructional abilities and frontotemporal atrophy on imaging studies. However, Family D has an earlier mean age of onset and shorter duration of disease than Families F and G (49.0 and 5.1 years versus 61-64 and 7.3-8.0 years, respectively). Two members of Families D and F had neuropathological studies demonstrating lobar atrophy, but the brain from Family D had prominent and diffuse circular, intra-neuronal, neurofibrillary tangles not seen in Family F. The brain from Family F had ballooned neurons typical of Pick's disease type B not found in Family D. A second autopsy from Family D showed neurofibrillary tangles in the brainstem with a distribution similar to that found in progressive supranuclear palsy. These three families demonstrate that a missense mutation in the exon 10 microtubule-binding domain of the tau protein gene can produce severe behavioural abnormalities with fronto-temporal lobar atrophy and microscopic tau pathology. However, the findings in these families also emphasize that additional unidentified environmental and/or genetic factors must be producing important phenotypic variability on the background of an identical mutation. Apolipoprotein E genotype does not appear to be such a factor influencing age of onset in this disease. Keywords : frontotemporal dementia; tau; mutations
TI - A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene ( P301L )
JF - Brain
DO - 10.1093/brain/122.4.741
DA - 1999-04-01
UR - https://www.deepdyve.com/lp/oxford-university-press/a-clinical-pathological-comparison-of-three-families-with-1DYkMd9AIi
SP - 741
EP - 756
VL - 122
IS - 4
DP - DeepDyve
ER -