Combined occurrence of a novel TOR1A and a THAP1 mutation in primary dystonia


  • Funding agencies: This study was supported by grants from Beijing Nature Science Foundation (710025, X.H. Wan), Dystonia Fund of Chinese Medical Foundation (F.B. Cheng), and China Scholarship Council (F.B. Cheng, 201206170031). K.G. was funded by the Deutsche Forschungsgemeinschaft, the IZKF of the University of Tuebingen and the Elitepostdoc Programme Baden Württemberg

  • Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online version of this article.



The ΔGAG deletion of the TOR1A gene (DYT1) is responsible for DYT1 dystonia. However, no other TOR1A mutation has been reported in the Chinese population.


Two hundred one dystonia patients without the ΔGAG deletion were screened for other mutations in TOR1A. Gene function changes were analyzed by subcellular distribution and luciferase reporter assay.


A novel TOR1A mutation (c.581A>T, p.Asp194Val) was found in a patient with early-onset segmental dystonia harboring a THAP1 mutation (c.539T>C, p.Leu180Ser). Overexpression of mutant TOR1A Asp194Val protein induces inclusion formation in SK-N-AS cell lines, and the repressive activity of the mutant THAP1 Leu180Ser protein on TOR1A gene expression is decreased compared with wild-type THAP1.


This is the first report about a dystonia patient harboring two distinct dystonia gene mutations. Functional analysis indicated a potential additive effect of these two mutations, which might provoke the occurrence of dystonic symptoms in this patient. © 2014 International Parkinson and Movement Disorder Society