Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia


We report the discovery of a mutation in the THAP1 gene in three Amish-Mennonite families with mixed-onset primary torsion dystonia (also known as DYT6 dystonia). Another mutation in a German family with primary torsion dystonia suggests that THAP1 mutations also cause dystonia in other ancestry groups. We demonstrate that the missense mutation impairs DNA binding, suggesting that transcriptional dysregulation may contribute to the phenotype of DYT6 dystonia.

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Figure 1: Indel F45fs73X mutation in THAP1.


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We wish to thank all participants in this study. We thank P. de Carvalho Aguiar, G. Senthil and S. Singh for technical help; B. Ford, A. Hunt, P. Greene, N. Huang, A. Leder, P. Raj Kapoor, R. Tabamo, K. Blatt, E. Chai, S. Chouinard, A. Deligtish, P. Kavanagh, M. Brin, N. Lubarr and M. San Luciano for help with examination of the families; J. Soto-Valencia, K. Habermann, E. Ohmann, G. Heiman, D. de Leon and C. Moskowitz for organizing and coordinating family visits; and J. Haines for sharing control Amish-Mennonite samples. This work was supported by research grants from the Dystonia Medical Research Foundation (L.J.O., S.B.B., R.S.-P.), the Bachmann-Strauss Dystonia and Parkinson Foundation (S.B.B., L.J.O.), the National Institute of Neurological Disorders and Stroke (NS26636, L.J.O. and S.B.B.; K23NS047256, R.S.-P.), the National Institute of Aging (AG19085, J. Haines) and the Aaron Aronov Family Foundation (S.B.B.).

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T.F. performed all of the molecular genetic studies and wrote the paper; D.R. collected samples and provided clinical information of the subjects; R.S.-P. and S.B.B. examined subjects and assigned clinical status; S.G. cloned the expression constructs and performed all experiments needed for the gel shift assays; M.E.E. designed and supervised the EMSA experiments; L.J.O. and S.B.B. designed and supervised the genetic studies; D.R., R.S.-P., S.G., M.E.E., S.B.B. and L.J.O. edited the manuscript.

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Correspondence to Laurie J Ozelius.

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Fuchs, T., Gavarini, S., Saunders-Pullman, R. et al. Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia. Nat Genet 41, 286–288 (2009).

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