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FTDP‐17: An early‐onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation
Author(s) -
Sperfeld Anne D.,
Collatz Michael B.,
Baier Hartmut,
Palmbach Markus,
Storch Alexander,
Schwarz Johannes,
Tatsch Klaus,
Reske Sven,
Joosse Marijke,
Heutink Peter,
Ludolph Albert C.
Publication year - 1999
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/1531-8249(199911)46:5<708::aid-ana5>3.0.co;2-k
Subject(s) - parkinsonism , frontotemporal dementia , missense mutation , mutation , genetics , dementia , neuroscience , tau protein , epilepsy , medicine , biology , disease , gene , pathology , alzheimer's disease
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.