Mutations in THAP1 have been associated with dystonia 6. THAP1 encodes a transcription factor with mostly unknown targets. We tested the hypothesis that THAP1 regulates the expression of DYT1 (TOR1A), another dystonia-causing gene. After characterization of the TOR1A promoter, we demonstrate that THAP1 binds to the core promoter of TOR1A. Further, we report that wild type THAP1 represses the expression of TOR1A, whereas dystonia 6-associated mutant THAP1 results in decreased repression of TOR1A. Our data demonstrate that THAP1 regulates the transcription of TOR1A, suggesting transcriptional dysregulation as a cause of dystonia.

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Posterior cortical atrophy (PCA) represents a degenerative disorder characterized by the development of higherorder visual deficit. 1 PCA may result from heterogeneous pathologies that make up tauopathies. An increasing number of mutations in the tau gene (microtubule-associated protein tau [MAPT]) causes a wide spectrum of clinical presentations known as frontotemporal dementia with parkinsonism linked to chromosome-17 (FTDP-17). 2 Symptomatology usually involves executive dysfunction and altered personality and behavior, with patients displaying parkinsonian features.We describe the case of a woman with PCA who further developed asymmetric motor signs. A mutation in the MAPT gene was detected, and a diagnosis of FTDP-17 was formulated. To our knowledge, this is the very first report of a patient suffering from FTDP-17 diagnosed with posterior cortical atrophy. Case ReportA 55-year-old woman started suffering in 2006 from altered perception of human faces. Initially the visual distortion was fluctuating; over the following year it became constant, and she could not recognize her husband and children by their faces anymore. She further developed visuospatial deficits, with difficulty in localizing stimuli, judging distances, or orienting herself in familiar surroundings. A first neurological examination revealed visual agnosia. She had no visual hallucinations or personality changes. Biochemical investigations and CSF analysis were normal. Her mother suffered from dementia that started when she was 80. Genetic tests for Alzheimer's disease genes (betaPP, PS1, PS2) were performed, revealing normal alleles.As the disease progressed, she developed difficulties manipulating objects with her left hand. On further neurological examination, she showed marked ocular apraxia, and she appeared to be cortically blind. Motor signs appeared and were confined to her left arm, with plastic rigidity, bradykinesia, and postural tremor; dopaminergic treatment was not tolerated.Brain magnetic resonance imaging (MRI) showed slight signal alteration in parieto-occipital white matter bilaterally without significant atrophy; an 18F-FDG PET brain study demonstrated decreased metabolism in the posterior parietal and occipital regions, compatible with PCA. To investigate