FTDP-17: An early-onset phenotype with parkinsonism and epileptic seizurescaused by a novel mutation

Recently, mutations in the tau gene on chromosome 17 were found causative f or autosomal dominantly inherited frontotemporal dementia and parkinsonism (FTDP-17). We describe a family carrying a missense mutation at nucleotide 1137 C --> T, resulting in the amino acid substitution P301S. Methods of in vestigations include clinical, electrophysiological, and imaging techniques . This kindred presents with a novel phenotype characterized by an early on set of rapidly progressive frontotemporal dementia and parkinsonism in comb ination with epileptic seizures. We define the dopaminergic deficits as bei ng predominantly presynaptic by the use of single-photon emission computed tomography with a dopamine transporter ligand. The association of this earl y-onset phenotype with P301S mutation is not entirely consistent with curre nt criteria for the diagnosis of frontotemporal dementias and may encourage the search for tau mutations in diseases similar but not identical to FTDP -17. Also, the change from proline to serine suggests that this mutation mi ght contribute to tau hyperphosphorylation.