title: DYT6 dystonia: mutation screening, phenotype, and response to deep brain stimulation.
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.
authors.affiliation: Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Justus L
authors.initials: JL
authors.lastname: Groen
authors.forename: Katja
authors.initials: K
authors.lastname: Ritz
authors.forename: Maria Fiorella
authors.initials: MF
authors.lastname: Contarino
authors.forename: Bart P
authors.initials: BP
authors.lastname: van de Warrenburg
authors.forename: Majid
authors.initials: M
authors.lastname: Aramideh
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Foncke
authors.forename: Jacobus J
authors.initials: JJ
authors.lastname: van Hilten
authors.forename: P Richard
authors.initials: PR
authors.lastname: Schuurman
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Speelman
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Koelman
authors.forename: Rob M A
authors.initials: RM
authors.lastname: de Bie
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.forename: Marina A
authors.initials: MA
authors.lastname: Tijssen
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D046690:Deep Brain Stimulation / Q000379:methods*; D004422:Dystonia Musculorum Deformans / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D005192:Family Health; D005260:Female; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D005917:Globus Pallidus / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C474080:THAP1 protein, human