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Direct interaction between causative genes of DYT1 and DYT6 primary dystonia

Authors

  • Sophie Gavarini PhD,

    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York
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  • Corinne Cayrol PhD,

    1. CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France
    2. Université de Toulouse, UPS, IPBS, Toulouse, France
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  • Tania Fuchs PhD,

    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York
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  • Natalia Lyons MSc,

    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York
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  • Michelle E. Ehrlich MD, PhD,

    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York
    2. Department of Pediatrics, Mount Sinai School of Medicine, New York, New York
    3. Department of Neurology, Mount Sinai School of Medicine, New York, New York
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  • Jean-Philippe Girard PhD,

    1. CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France
    2. Université de Toulouse, UPS, IPBS, Toulouse, France
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    • J.-P.G. and L.J.O. are co-senior authors.

  • Laurie J. Ozelius PhD

    Corresponding author
    1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York
    2. Department of Pediatrics, Mount Sinai School of Medicine, New York, New York
    3. Department of Neurology, Mount Sinai School of Medicine, New York, New York
    • Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029 or Jean-Philippe Girard, CNRS-IPBS, 205 route de Narbonne, 31077 Toulouse, France
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    • J.-P.G. and L.J.O. are co-senior authors.


Abstract

Primary dystonia is a movement disorder characterized by sustained muscle contractions and in which dystonia is the only or predominant clinical feature. TOR1A(DYT1) and the transcription factor THAP1(DYT6) are the only genes identified thus far for primary dystonia. Using electromobility shift assays and chromatin immunoprecipitation (ChIP) quantitative polymerase chain reaction (qPCR), we demonstrate a physical interaction between THAP1 and the TOR1A promoter that is abolished by pathophysiologic mutations. Our findings provide the first evidence that causative genes for primary dystonia intersect in a common pathway and raise the possibility of developing novel therapies targeting this pathway. Ann Neurol 2010

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