Mutation screening of the DYT6/THAP1 gene in Serbian patients with primary dystonia
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Primary dystonia (PrD) is characterized by sustained muscle contractions, causing twisting and repetitive movements and abnormal postures. Besides DYT1/TOR1A gene, DYT6/THAP1 gene is the second gene known to cause primary pure dystonia. We screened 281 Serbian primary dystonia patients and 106 neurologically healthy control individuals for the GAG deletion in TOR1A gene and for mutations in THAP1 gene by direct sequencing. Nine subjects were found to have the GAG deletion in TOR1A gene. Four coding mutations, including two novel mutations, were identified in the THAP1 gene in five unrelated patients. Two mutations were missense, one was nonsense, and one was 24 bp duplication. None of the coding mutations were seen in 106 control individuals. In addition, one novel nucleotide change in the 5′UTR region of THAP1 gene was detected in two unrelated patients. The mutation frequency of THAP1 gene in Serbian patients with primary dystonia was 1.8 %, similar to the mutation frequency in other populations. Most of the patients reported here with THAP1 mutations had the clinical features of predominantly laryngeal or oromandibular dystonia. Our data expand the genotypic spectrum of THAP1 and strengthen the association with upper body involvement, including the cranial and cervical regions that are usually spared in DYT1-PrD.
KeywordsDYT6 THAP1 Dystonia Clinical manifestation
This study was supported by a grant from the Ministry of Education and Science, Republic of Serbia (projects no. ON175090 and ON175091). The authors declare that they have no conflict of interest.
Conflicts of interest
This study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
Online Resource 1.mpg : Patient1 (Table 1): oro-lingual dystonia, torticollis, disarrthria without spasmodic dysphonia, dystonic posture of both arms (more prominent on the left arm) and mild feet dystonia
Online Resource 2.mpg : Patient 2 (Table 1): severe left foot dystonia and reduced right arm swing
Online Resource 3.mpg : Patient 4 (Table 1): generalized dystonia with severe spasmodic dysphoni
Online Resource 4.mpg: Patient 5 (Table 1): dystonic posture of arms with myoclonic jerks of the right arm, and severe writer’s cramp
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