From genotype to phenotype: a clinical pathological, and biochemical investigation of frontotemporal dementia and parkinsonism (FTDP-17) caused by the P301L tau mutation.

摘要: Frontotemporal dementia is a heterogeneous, often inherited disorder that typically presents with the insidious onset of behavioral and personality changes. Two genetic loci have been identified mutations in tau causally implicated subset families linked to one these on chromosome 17q21-22. In this study, linkage analysis was performed large pedigree, MN family, suggesting 17q21-22 linkage. Mutational coding region C-to-T change exon 10 resulted conversion proline leucine (P301L) segregated frontotemporal family. The clinical pathological findings family emphasize significant overlap between Pick's disease, corticobasal degeneration, challenge some current dogma surrounding condition. Pathological studies two brains from affected members Family obtained at autopsy demonstrate numerous tau-positive inclusions were most prominent frontal lobes, anterior temporal brainstem structures, as well Pick-like bodies associated granulovacuolar degeneration. These observed 1 patient motor neuron disease. Because present only mRNA for protein four microtubule binding repeats (4R), mutation should selectively affect 4Rtau isoforms. Indeed, immunoblotting demonstrated insoluble aggregated both gray white matter individuals. Although there similarity 2 cases, pattern degenerative changes not identical, other or epigenetic factors can significantly modify regional topology neurodegeneration