title: Mutation screening of the DYT6/THAP1 gene in Serbian patients with primary dystonia.
abstract: 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.
authors.affiliation: Institute of Neurology CCS, School of Medicine, University of Belgrade, Dr Subotića 6, 11000 Belgrade, Serbia.
authors.forename: Valerija S
authors.initials: VS
authors.lastname: Dobričić
authors.forename: Nikola D
authors.initials: ND
authors.lastname: Kresojević
authors.forename: Marina V
authors.initials: MV
authors.lastname: Svetel
authors.forename: Milena Z
authors.initials: MZ
authors.lastname: Janković
authors.forename: Igor N
authors.initials: IN
authors.lastname: Petrović
authors.forename: Aleksandra D
authors.initials: AD
authors.lastname: Tomić
authors.forename: Ivana V
authors.initials: IV
authors.lastname: Novaković
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Kostić
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D020821:Dystonic Disorders / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D055771:Serbia / Q000453:epidemiology; D018911:Trinucleotide Repeats / Q000235:genetics*; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C474080:THAP1 protein, human