Commentary| Volume 79, ISSUE 5, P341-342, March 01, 2016

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What Makes You Tic? A New Lead in Tourette Syndrome Genetics

  • Thomas V. Fernandez
    Address correspondence to Thomas V. Fernandez, M.D., Yale University School of Medicine, Yale Child Study Center, 230 S Frontage Road, New Haven, CT 06520.
    Child Study Center and Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
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      Gilles de la Tourette syndrome (GTS) is a developmental neuropsychiatric disorder characterized by motor and vocal tics that can range in severity from mild to disabling. Despite accumulated evidence for a substantial genetic contribution to disease risk, gene discovery in GTS has been challenging. Decades of candidate gene association studies initially reporting positive findings have failed to replicate in larger patient cohorts, and genome-wide association studies have yet to generate statistically significant signals. As in other complex neurodevelopmental disorders, specific risk genes have been more difficult to identify than initially anticipated, particularly given early data interpreted to suggest that GTS was a single-gene autosomal dominant disorder. Rather, it seems most likely that risk for GTS is mediated by a conspiracy of multiple genes harboring small-effect common variants and large-effect rare variants, combined with environmental and epigenetic influences (
      • Richer P.
      • Fernandez T.V.
      Tourette syndrome: Bridging the gap between genetics and biology.
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      Linked Article

      • Association of AADAC Deletion and Gilles de la Tourette Syndrome in a Large European Cohort
        Biological PsychiatryVol. 79Issue 5
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          Gilles de la Tourette syndrome (GTS) is a complex neuropsychiatric disorder with a strong genetic influence where copy number variations are suggested to play a role in disease pathogenesis. In a previous small-scale copy number variation study of a GTS cohort (n = 111), recurrent exon-affecting microdeletions of four genes, including the gene encoding arylacetamide deacetylase (AADAC), were observed and merited further investigations.
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