DYT6 dystonia: Review of the literature and creation of the UMD locus-specific database (LSDB) for mutations in the THAP1 gene

Authors

  • Arnaud Blanchard,

    1. INSERM U827, Montpellier, F-34000, France
    2. Université Montpellier1, UFR de Médecine, Montpellier, F-34000, France
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  • Vuthy Ea,

    1. INSERM U827, Montpellier, F-34000, France
    2. Université Montpellier1, UFR de Médecine, Montpellier, F-34000, France
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  • Agathe Roubertie,

    1. INSERM U827, Montpellier, F-34000, France
    2. Université Montpellier1, UFR de Médecine, Montpellier, F-34000, France
    3. CHU Montpellier, Hôpital Gui de Chauliac, Service de Neuropédiatrie, Montpellier, F-34000, France
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  • Mélanie Martin,

    1. INSERM U827, Montpellier, F-34000, France
    2. Université Montpellier1, UFR de Médecine, Montpellier, F-34000, France
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  • Coline Coquart,

    1. CHU Montpellier, Hôpital Arnaud de Villeneuve, Laboratoire de Génétique Moléculaire, Montpellier, F-34000, France
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  • Mireille Claustres,

    1. INSERM U827, Montpellier, F-34000, France
    2. Université Montpellier1, UFR de Médecine, Montpellier, F-34000, France
    3. CHU Montpellier, Hôpital Arnaud de Villeneuve, Laboratoire de Génétique Moléculaire, Montpellier, F-34000, France
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  • Christophe Béroud,

    1. INSERM U827, Montpellier, F-34000, France
    2. Université Montpellier1, UFR de Médecine, Montpellier, F-34000, France
    3. CHU Montpellier, Hôpital Arnaud de Villeneuve, Laboratoire de Génétique Moléculaire, Montpellier, F-34000, France
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  • Gwenaëlle Collod-Béroud

    Corresponding author
    1. INSERM U827, Montpellier, F-34000, France
    2. Université Montpellier1, UFR de Médecine, Montpellier, F-34000, France
    • INSERM U827, Institut Universitaire de Recherche Clinique, 641 av du doyen Gaston Giraud, 34093 Montpellier cedex 5, France.
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  • Communicated by Alastair F. Broun

Abstract

By family-based screening, first Fuchs and then many other authors showed that mutations in THAP1 (THAP [thanatos-associated protein] domain-containing, apoptosis-associated protein 1) account for a substantial proportion of familial, early-onset, nonfocal, primary dystonia cases (DYT6 dystonia). THAP1 is the first transcriptional factor involved in primary dystonia and the hypothesis of a transcriptional deregulation, which was primarily proposed for the X-linked dystonia-parkinsonism (DYT3 dystonia), provided thus a new way to investigate the possible mechanism underlying the development of dystonic movements. Currently, 56 families present with a THAP1 mutation; however, no genotype/phenotype relationship has been found. Therefore, we carried out a systematic review of the literature on the THAP1 gene to colligate all reported patients with a specific THAP1 mutation and the associated clinical signs in order to describe the broad phenotypic continuum of this disorder. To facilitate the comparison of the identified mutations, we created a Locus-Specific Database (UMD-THAP1 LSDB) available at http://www.umd.be/THAP1/. Currently, the database lists 56 probands and 43 relatives with the associated clinical phenotype when available. The identification of a larger number of THAP1 mutations and collection of high-quality clinical information for each described mutation through international collaborative effort will help investigating the structure–function and genotype–phenotype correlations in DYT6 dystonia. Hum Mutat 32:1213–1224, 2011. ©2011 Wiley Periodicals, Inc.

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