DYT6 dystonia: review of the literature and creation of the UMD Locus-Specific Database (LSDB) for mutations in the THAP1 gene

Hum Mutat. 2011 Nov;32(11):1213-24. doi: 10.1002/humu.21564. Epub 2011 Sep 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis Regulatory Proteins / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Databases, Genetic*
  • Dystonia Musculorum Deformans / genetics*
  • Female
  • Genetic Association Studies
  • Humans
  • Male
  • Mutation*
  • Nuclear Proteins / genetics*
  • Young Adult


  • Apoptosis Regulatory Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • THAP1 protein, human

Supplementary concepts

  • Dystonia 6, torsion