title: FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation.
abstract: Recently, mutations in the tau gene on chromosome 17 were found causative for 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 investigations include clinical, electrophysiological, and imaging techniques. This kindred presents with a novel phenotype characterized by an early onset of rapidly progressive frontotemporal dementia and parkinsonism in combination with epileptic seizures. We define the dopaminergic deficits as being predominantly presynaptic by the use of single-photon emission computed tomography with a dopamine transporter ligand. The association of this early-onset phenotype with P301S mutation is not entirely consistent with current 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 might contribute to tau hyperphosphorylation.
authors.affiliation: Department of Neurology, University of Ulm, Germany.
authors.forename: A D
authors.initials: AD
authors.lastname: Sperfeld
authors.forename: M B
authors.initials: MB
authors.lastname: Collatz
authors.forename: H
authors.initials: H
authors.lastname: Baier
authors.forename: M
authors.initials: M
authors.lastname: Palmbach
authors.forename: A
authors.initials: A
authors.lastname: Storch
authors.forename: J
authors.initials: J
authors.lastname: Schwarz
authors.forename: K
authors.initials: K
authors.lastname: Tatsch
authors.forename: S
authors.initials: S
authors.lastname: Reske
authors.forename: M
authors.initials: M
authors.lastname: Joosse
authors.forename: P
authors.initials: P
authors.lastname: Heutink
authors.forename: A C
authors.initials: AC
authors.lastname: Ludolph
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D019943:Amino Acid Substitution; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D003704:Dementia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D004569:Electroencephalography; D004827:Epilepsy / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D010641:Phenotype; D013702:Temporal Lobe / Q000473:pathology; D015899:Tomography, Emission-Computed, Single-Photon; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D016875:tau Proteins