• Open Access

THAP1 mutations and dystonia phenotypes: Genotype phenotype correlations§

Authors

  • Georgia Xiromerisiou MD,

    Corresponding author
    1. Department of Molecular Neuroscience and Reta Lila Weston Institute, University College London Institute of Neurology, London, London, United Kingdom
    2. Department of Neurology, Faculty of Medicine University of Thessaly, Larissa, Greece
    • Department of Neurology, Faculty of Medicine, University of Thessaly, Biopolis, Mezourlo Hill, 41100 Larissa, Greece
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  • Henry Houlden MD,

    1. Department of Molecular Neuroscience and Reta Lila Weston Institute, University College London Institute of Neurology, London, London, United Kingdom
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  • Nikolaos Scarmeas MD,

    1. Taub Institute, Sergievsky Center, Department of Neurology, Columbia University, New York, New York, USA
    2. Department of Neurology, Medical School of National and Kapodistrian University of Athens, Athens, Greece
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  • Maria Stamelou MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, London, United Kingdom
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  • Eleanna Kara MD,

    1. Department of Molecular Neuroscience and Reta Lila Weston Institute, University College London Institute of Neurology, London, London, United Kingdom
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  • John Hardy PhD,

    1. Department of Molecular Neuroscience and Reta Lila Weston Institute, University College London Institute of Neurology, London, London, United Kingdom
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  • Andrew J. Lees MD,

    1. Department of Molecular Neuroscience and Reta Lila Weston Institute, University College London Institute of Neurology, London, London, United Kingdom
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  • Prasad Korlipara MD,

    1. Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, London, United Kingdom
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  • Patricia Limousin MD,

    1. Unit of Functional Neurosurgery, Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, University College London, London, United Kingdom
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  • Reema Paudel MS,

    1. Department of Molecular Neuroscience and Reta Lila Weston Institute, University College London Institute of Neurology, London, London, United Kingdom
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  • Georgios M. Hadjigeorgiou MD,

    1. Department of Neurology, Faculty of Medicine University of Thessaly, Larissa, Greece
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  • Kailash P. Bhatia MD

    1. Sobell Department of Motor Neuroscience and Movement Disorders, University College London Institute of Neurology, London, United Kingdom
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  • Funding agencies: This work was supported by The Medical Research Council, The Wellcome Trust, The Dystonia Medical Research Foundation, the Parkinson's Disease Foundation, The Brain Research Trust, and the National Institute for Health Research University College London Hospitals/University College London Comprehensive Biomedical Research Center.

  • Relative conflicts of interest/financial disclosures: Nothing to report.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

THAP1 mutations have been shown to be the cause of DYT6. A number of different mutation types and locations in the THAP1 gene have been associated with a range of severity and dystonia phenotypes, but, as yet, it has been difficult to identify clear genotype phenotype patterns. Here, we screened the THAP1 gene in a further series of dystonia cases and evaluated the mutation pathogenicity in this series as well as previously reported mutations to investigate possible phenotype-genotype correlations. THAP1 mutations have been identified throughout the coding region of the gene, with the greatest concentration of variants localized to the THAP1 domain. In the additional cases analyzed here, a further two mutations were found. No obvious, indisputable genotype-phenotype correlation emerged from these data. However, we managed to find a correlation between the pathogenicity of mutations, distribution, and age of onset of dystonia. THAP1 mutations are an important cause of dystonia, but, as yet, no clear genotype-phenotype correlations have been identified. Greater mutation numbers in different populations will be important and mutation-specific functional studies will be essential to identify the pathogenicity of the various THAP1 mutations. © 2012 Movement Disorder Society

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