Search for a mutation in the tau gene in a Swiss family with frontotemporal dementia

Frontotemporal dementia (FTD) is considered to have a heterogeneous aetiolo gy. To date the tau gene located on chromosome 17 has been shown to be impl icated in the pathogenesis of several FTD families with parkinsonism, the s o called FTDP-17 families. The mutations reported so far are located within exons 9 to 13, a region coding for the microtubule-binding sites. They are causing various cytoskeletal disturbances. We are describing here the main clinical and neuropathological features of a Swiss FTD family with members presenting a FTDP-like clinical phenotype. However, if we except two silen t polymorphic sites at position 227 and 255 in exon 9, neither a known FTDP -17 mutation nor a novel one was detected in this region of the tau gene. T hus, the existence of a yet unknown mechanism of neurodegeneration, other t han via mutations near or within the microtubule-binding sites, or the exon 10 splice sites of the tau gene, has to be considered to explain dementia in this family. A mutation in another gene is still possible. (C) 2000 Acad emic Press.