Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

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

Nature Genetics volume 41, pages 286–288 (2009)Cite this article

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Indel F45fs73X mutation in THAP1.

Similar content being viewed by others

References

  1. Fahn, S. Adv Neurol. 50, 1–8 (1988).

    Article  CAS  Google Scholar 

  2. de Carvalho Aguiar, P.M. & Ozelius, L.J. Lancet Neurol. 1, 316–325 (2002).

    Article  Google Scholar 

  3. Ozelius, L.J. et al. Nat. Genet. 17, 40–48 (1997).

    Article  CAS  Google Scholar 

  4. Almasy, L. et al. Ann. Neurol. 42, 670–673 (1997).

    Article  CAS  Google Scholar 

  5. Saunders-Pullman, R. et al. Am. J. Med. Genet. A. 143A, 2098–2105 (2007).

    Article  CAS  Google Scholar 

  6. Kramer, P.L. et al. Am. J. Hum. Genet. 55, 468–475 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Clouaire, T. et al. Proc. Natl. Acad. Sci. USA 102, 6907–6912 (2005).

    Article  CAS  Google Scholar 

  8. Roussigne, M., Cayrol, C., Clouaire, T., Amalric, F. & Girard, J.P. Oncogene 22, 2432–2442 (2003).

    Article  CAS  Google Scholar 

  9. Roussigne, M. et al. Trends Biochem. Sci. 28, 66–69 (2003).

    Article  CAS  Google Scholar 

  10. Cayrol, C. et al. Blood 109, 584–594 (2007).

    Article  CAS  Google Scholar 

  11. Duan, W., Zhang, Z., Gash, D.M. & Mattson, M.P. Ann. Neurol. 46, 587–597 (1999).

    Article  CAS  Google Scholar 

  12. Bessiere, D. et al. J. Biol. Chem. 283, 4352–4363 (2008).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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.).

Author information

Authors and Affiliations

  1. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, 10029, New York, USA

    Tania Fuchs, Sophie Gavarini & Laurie J Ozelius

  2. Department of Neurology, Beth Israel Medical Center, New York, 10003, New York, USA

    Rachel Saunders-Pullman, Deborah Raymond & Susan B Bressman

  3. Department of Neurology, Albert Einstein College of Medicine, Bronx, 10461, New York, USA

    Rachel Saunders-Pullman & Susan B Bressman

  4. Department of Neurology, Mount Sinai School of Medicine, New York, 10029, New York, USA

    Michelle E Ehrlich & Laurie J Ozelius

  5. Department of Pediatric, Mount Sinai School of Medicine, New York, 10029, New York, USA

    Michelle E Ehrlich

Authors
  1. Tania Fuchs
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sophie Gavarini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rachel Saunders-Pullman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Deborah Raymond
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michelle E Ehrlich
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Susan B Bressman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Laurie J Ozelius
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Corresponding author

Correspondence to Laurie J Ozelius.

Supplementary information

Supplementary Text and Figures

Supplementary Methods and Supplementary Figures 1–3 (PDF 233 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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). https://doi.org/10.1038/ng.304

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng.304

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing