Movement Disorders (revue)

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DYT6 dystonia: Mutation screening, phenotype, and response to deep brain stimulation

Identifieur interne : 001D66 ( Main/Exploration ); précédent : 001D65; suivant : 001D67

DYT6 dystonia: Mutation screening, phenotype, and response to deep brain stimulation

Auteurs : Justus L. Groen [Pays-Bas] ; Katja Ritz [Pays-Bas] ; Maria Fiorella Contarino [Pays-Bas] ; Bart P. Van De Warrenburg [Pays-Bas] ; Majid Aramideh [Pays-Bas] ; Elisabeth M. Foncke [Pays-Bas] ; Jacobus J. Van Hilten [Pays-Bas] ; P. Richard Schuurman [Pays-Bas] ; Johannes D. Speelman [Pays-Bas] ; Johannes H. Koelman [Pays-Bas] ; Rob M. A. De Bie [Pays-Bas] ; Frank Baas [Pays-Bas] ; Marina A. Tijssen [Pays-Bas]

Source :

RBID : ISTEX:A81611ACD121D9D0B4B3A97C9AEBDF90E513EF82

Descripteurs français

English descriptors

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

Url:
DOI: 10.1002/mds.23285


Affiliations:


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Le document en format XML

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<term>Adolescent</term>
<term>Adult</term>
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<term>Apoptosis Regulatory Proteins (genetics)</term>
<term>Cohort Studies</term>
<term>DNA-Binding Proteins (genetics)</term>
<term>DYT6</term>
<term>Deep Brain Stimulation (methods)</term>
<term>Deep brain stimulation</term>
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<term>Dystonia Musculorum Deformans (genetics)</term>
<term>Dystonia Musculorum Deformans (physiopathology)</term>
<term>Dystonia Musculorum Deformans (therapy)</term>
<term>Family Health</term>
<term>Female</term>
<term>Genetic Testing (methods)</term>
<term>Genotype</term>
<term>Globus Pallidus (physiology)</term>
<term>Humans</term>
<term>Male</term>
<term>Medical screening</term>
<term>Middle Aged</term>
<term>Mutation</term>
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<term>Nervous system diseases</term>
<term>Netherlands (epidemiology)</term>
<term>Nuclear Proteins (genetics)</term>
<term>Phenotype</term>
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<term>Young Adult</term>
<term>deep brain stimulation</term>
<term>genetic screening</term>
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<term>Mutation</term>
<term>Pathologie du système nerveux</term>
<term>Phénotype</term>
<term>Stimulation cérébrale profonde</term>
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<div type="abstract" xml:lang="en">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</div>
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