title: DYT6 dystonia: review of the literature and creation of the UMD Locus-Specific Database (LSDB) for mutations in the THAP1 gene.
abstract: By family-based screening, first Fuchs and then many other authors showed that mutations in THAP1 (THAP [thanatos-associated protein] domain-containing, apoptosis-associated protein 1) account for a substantial proportion of familial, early-onset, nonfocal, primary dystonia cases (DYT6 dystonia). THAP1 is the first transcriptional factor involved in primary dystonia and the hypothesis of a transcriptional deregulation, which was primarily proposed for the X-linked dystonia-parkinsonism (DYT3 dystonia), provided thus a new way to investigate the possible mechanism underlying the development of dystonic movements. Currently, 56 families present with a THAP1 mutation; however, no genotype/phenotype relationship has been found. Therefore, we carried out a systematic review of the literature on the THAP1 gene to colligate all reported patients with a specific THAP1 mutation and the associated clinical signs in order to describe the broad phenotypic continuum of this disorder. To facilitate the comparison of the identified mutations, we created a Locus-Specific Database (UMD-THAP1 LSDB) available at http://www.umd.be/THAP1/. Currently, the database lists 56 probands and 43 relatives with the associated clinical phenotype when available. The identification of a larger number of THAP1 mutations and collection of high-quality clinical information for each described mutation through international collaborative effort will help investigating the structure-function and genotype-phenotype correlations in DYT6 dystonia.
authors.affiliation: INSERM U827, Montpellier, F-34000, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Blanchard
authors.forename: Vuthy
authors.initials: V
authors.lastname: Ea
authors.forename: Agathe
authors.initials: A
authors.lastname: Roubertie
authors.forename: Mélanie
authors.initials: M
authors.lastname: Martin
authors.forename: Coline
authors.initials: C
authors.lastname: Coquart
authors.forename: Mireille
authors.initials: M
authors.lastname: Claustres
authors.forename: Christophe
authors.initials: C
authors.lastname: Béroud
authors.forename: Gwenaëlle
authors.initials: G
authors.lastname: Collod-Béroud
mesh_terms: D000293:Adolescent; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D030541:Databases, Genetic; D004422:Dystonia Musculorum Deformans / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C474080:THAP1 protein, human