DYT6 dystonia: Mutation screening,phenotype, and response to deep brain stimulation |
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| Authors: | Justus L Groen MD Katja Ritz MSc Maria Fiorella Contarino MD Bart P van de Warrenburg MD PhD Majid Aramideh MD PhD Elisabeth M Foncke MD PhD Jacobus J van Hilten MD PhD P Richard Schuurman MD PhD Johannes D Speelman MD PhD Johannes H Koelman MD PhD Rob MA de Bie MD PhD Frank Baas MD PhD Marina A Tijssen MD PhD |
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| Institution: | 1. Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;2. Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;3. Department of Neurology, Donders Centre for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands;4. Department of Neurology, Medical Centre Alkmaar, Alkmaar, The Netherlands;5. Department of Neurology, VU University Medical Centre, Amsterdam, The Netherlands;6. Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands;7. Department of Neurosurgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands |
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| Abstract: | Mutations in THAP1, a gene encoding a nuclear pro‐apoptotic protein, have been associated with DYT6 dystonia. First reports on the phenotype of DYT6 dystonia show an early onset dystonia with predominant cranio‐cervical and laryngeal involvement. Here we assessed the frequency and phenotype of THAP1 mutation carriers in a large Dutch cohort of adult‐onset (≥26 years) dystonia (n = 388) and early‐onset dystonia (n = 67) patients. We describe the phenotype of DYT6 dystonia patients and their response on GPi DBS. Overall, 3 nonsynonymous heterozygous mutations were detected in the early‐onset group (4.5%). Two DYT6 families were identified, showing a heterozygous phenotype. All patients had segmental or generalized dystonia, often associated with profound oromandibular and laryngeal involvement. No nonsynonymous mutations were found in patients with adult‐onset focal dystonia. Rare synonymous variants were identified in conserved regions of THAP1, two in the adult‐onset cervical dystonia group and one in the control group. Four DYT6 dystonia patients were treated with GPi DBS with moderate to good response on motor function but marginal benefit on speech. © 2010 Movement Disorder Society |
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| Keywords: | DYT6 THAP1 genetic screening deep brain stimulation |
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