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Houlden, H; Schneider, SA; Paudel, R; Melchers, A; Schwingenschuh, P; Edwards, M; Hardy, J; Bhatia, KP.
THAP1 mutations (DYT6) are an additional cause of early-onset dystonia.
Neurology. 2010; 74(10): 846-850. Doi: 10.1212/WNL.0b013e3181d5276d [OPEN ACCESS]
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Co-authors Med Uni Graz: Schwingenschuh Petra
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Abstract:: Background: The clinical phenotype of DYT6 consists mainly of primary craniocervical dystonia. Recently, the THAP1 gene was identified as the cause of DYT6, where a total of 13 mutations have been identified in Amish-Mennonite and European families. Methods: We sequenced the THAP1 gene in a series of 362 British, genetically undetermined, primary dystonia patients (78 with focal, 186 with segmental, and 98 with generalized dystonia) and in 28 dystonia-manifesting DYT1 patients and 176 normal control individuals. Results: Nine coding mutations were identified in the THAP1 gene. Two were small deletions, 2 were nonsense, and 5 were missense. Eight mutations were heterozygous, and 1 was homozygous. The main clinical presentation of cases with THAP1 mutations was early-onset (<30 years) dystonia in the craniocervical region or the limbs (8 of 9 patients). There was phenotypic variability with laryngeal or oromandibular dystonia present in 3 cases. Four of 9 THAP1 cases developed generalized dystonia. Conclusions: The number of THAP1 mutations has been significantly expanded, indicating an uncommon but important cause of dystonia. Coding mutations account for 9 of 362 dystonia cases, indicating a mutation frequency of 2.5% of dystonia cases in the population that we have screened. The majority of cases reported here with THAP1 mutations had craniocervical-or limb-onset segmental dystonia, but we also identified 1 homozygous THAP1 mutation, associated initially with writer's dystonia and then developing segmental dystonia. Three of our patients had a nonsense or frameshift THAP1 mutation and the clinical features of laryngeal or oromandibular dystonia. These data suggest that early-onset dystonia that includes the involvement of the larynx or face is frequently associated with THAP1 mutations. Neurology (R) 2010; 74: 846-850
Find related publications in this database (using NLM MeSH Indexing): Adult -; Age of Onset -; Aged -; Aged, 80 and over -; Apoptosis Regulatory Proteins - genetics; Chi-Square Distribution -; DNA Mutational Analysis -; DNA-Binding Proteins - genetics; Dystonia - genetics; Family Health -; Female -; Genetic Predisposition to Disease - genetics; Humans -; Male -; Middle Aged -; Nuclear Proteins - genetics; Polymorphism, Genetic - genetics