ArticleThe Lancet. Neurology2009
Mutations in THAP1 (DYT6) and generalised dystonia with prominent spasmodic dysphonia: a genetic screening study.
Article in The Lancet. Neurology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 146 citations in OpenAlex.
- Laryngeal dystonia: a comprehensive review of aetiology, clinical presentation, diagnosis, and treatment approaches.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Review
- Assessing vocal changes through spectral analyses of vocalizations in a cerebellar-specific dystonia mouse model.Dystonia (Lausanne, Switzerland) · 2026Article
- Spasmodic Dysphonia.World journal of otorhinolaryngology - head and neck surgery · 2025Review
- Generalized dystonia unraveled: Molecular mechanisms, diagnostic strategies, and treatment paradigms.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Pediatric Genetic Dystonias: Current Diagnostic Approaches and Treatment Options.Life (Basel, Switzerland) · 2025Review
- Cerebellar contributions to dystonia: unraveling the role of Purkinje cells and cerebellar nuclei.Dystonia (Lausanne, Switzerland) · 2025Article
- GPi DBS treatment outcome in children with monogenic dystonia: a case series and review of the literature.Frontiers in neurology · 2023Article
- Dystonia Diagnosis: Clinical Neurophysiology and Genetics.Journal of clinical medicine · 2022Review
- The Patho-Neurophysiological Basis and Treatment of Focal Laryngeal Dystonia: A Narrative Review and Two Case Reports Applying TMS over the Laryngeal Motor Cortex.Journal of clinical medicine · 2022Review
- Pharmacological perturbation reveals deficits in D2 receptor responses in Thap1 null mice.Annals of clinical and translational neurology · 2021Article
- The dystonia gene THAP1 controls DNA double-strand break repair choice.Molecular cell · 2021Article
- Oromandibular and Laryngeal Dystonia Secondary to Dystonia 6 Due to THAP1 Variant in a Child.Indian journal of pediatrics · 2021Article
- Isolated dystonia: clinical and genetic updates.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Reduced Expression of GABAFrontiers in cell and developmental biology · 2021Article
- DYT6 Dystonia Mimicking Adolescent Idiopathic Scoliosis Successfully Treated by Pallidal Stimulation.International medical case reports journal · 2021Article
- Diverse Mechanisms Lead to Common Dysfunction of Striatal Cholinergic Interneurons in Distinct Genetic Mouse Models of Dystonia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Recent advances in understanding and managing dystonia.F1000Research · 2018Review
- Reversal of Status Dystonicus after Relocation of Pallidal Electrodes in DYT6 Generalized Dystonia.Tremor and other hyperkinetic movements (New York, N.Y.) · 2018Article
- Risk Factor Genes in Patients with Dystonia: A Comprehensive Review.Tremor and other hyperkinetic movements (New York, N.Y.) · 2018Review
- Clinical Management of Dystonia in Childhood.Paediatric drugs · 2017Review
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Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDYT6 is a primary, early-onset torsion dystonia; however, unlike in DYT1 dystonia, the symptoms of DYT6 dystonia frequently involve the craniocervical region. Recently, two mutations in THAP1, the gene that encodes THAP (thanatos-associated protein) domain-containing apoptosis-associated protein 1 (THAP1), have been identified as a cause of DYT6 dystonia.
methodsWe screened THAP1 by sequence analysis and quantitative real-time polymerase chain reaction (PCR) in 160 white patients of European ancestry who had dystonia with an early age at onset (n=64), generalised dystonia (n=35), a positive family history of dystonia (n=56), or facial or laryngeal dystonia. Another 160 patients with dystonia were screened for reported and novel variants in THAP1. 280 neurologically healthy controls were screened for the newly identified and previously reported changes in THAP1 and these and an additional 75 controls were screened for a rare non-coding mutation.
findingsWe identified two mutations in THAP1 (388_389delTC and 474delA), respectively, in two (1%) German patients from the 160 patients with dystonia. Both mutation carriers had laryngeal dystonia that started in childhood and both went on to develop generalised dystonia. Thus, two of three patients with early-onset generalised dystonia with orobulbar involvement had mutations in THAP1. One of the identified patients with DYT6 dystonia had two family members with subtle motor signs who also carried the same mutation. A rare substitution in the 5'untranslated region (-236_235GA-->TT) was found in 20 of 320 patients and in seven of 355 controls (p=0.0054).
interpretationAlthough mutations in THAP1 might have only a minor role in patients with different, but mainly focal, forms of dystonia, they do seem to be associated with early-onset generalised dystonia with spasmodic dysphonia. This combination of symptoms might be a characteristic feature of DYT6 dystonia and could be useful in the differential diagnosis of DYT1, DYT4, DYT12, and DYT17 dystonia. In addition to the identified mutations, a rare non-coding substitution in THAP1 might increase the risk of dystonia.
fundingDeutsche Forschungsgemeinschaft; Volkswagen Foundation; Dystonia Medical Research Foundation; University of Lübeck.
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