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Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia.

Publication ,  Journal Article
Calakos, N; Patel, VD; Gottron, M; Wang, G; Tran-Viet, K-N; Brewington, D; Beyer, JL; Steffens, DC; Krishnan, RR; Züchner, S
Published in: J Med Genet
September 2010

BACKGROUND: TOR1A encodes a chaperone-like AAA-ATPase whose Delta GAG (Delta E) mutation is responsible for an early onset, generalised dystonia syndrome. Because of the established role of the TOR1A gene in heritable generalised dystonia (DYT1), a potential genetic contribution of TOR1A to the more prevalent and diverse presentations of late onset, focal dystonia has been suggested. RESULTS: A novel TOR1A missense mutation (c.613T-->A, p.F205I) in a patient with late onset, focal dystonia is reported. The mutation occurs in a highly evolutionarily conserved region encoding the AAA-ATPase domain. Expression assays revealed that expression of F205I or Delta E, but not wildtype TOR1A, produced frequent intracellular inclusions. CONCLUSIONS: A novel, rare TOR1A variant has been identified in an individual with late onset, focal dystonia and evidence provided that the mutation impairs TOR1A function. Together these findings raise the possibility that this novel TOR1A variant may contribute to the expression of dystonia. In light of these findings, a more comprehensive genetic effort is warranted to identify the role of this and other rare TOR1A variants in the expression of late onset, focal dystonia.

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Published In

J Med Genet

DOI

EISSN

1468-6244

Publication Date

September 2010

Volume

47

Issue

9

Start / End Page

646 / 650

Location

England

Related Subject Headings

  • Mutation
  • Molecular Sequence Data
  • Molecular Chaperones
  • Middle Aged
  • Inclusion Bodies
  • Humans
  • Genetics & Heredity
  • Dystonic Disorders
  • Cell Line
  • Amino Acid Substitution
 

Citation

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Calakos, N., Patel, V. D., Gottron, M., Wang, G., Tran-Viet, K.-N., Brewington, D., … Züchner, S. (2010). Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia. J Med Genet, 47(9), 646–650. https://doi.org/10.1136/jmg.2009.072082
Calakos, Nicole, Viren D. Patel, Melissa Gottron, Gaofeng Wang, Khan-Nhat Tran-Viet, Danielle Brewington, John L. Beyer, David C. Steffens, Ranga R. Krishnan, and Stephan Züchner. “Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia.J Med Genet 47, no. 9 (September 2010): 646–50. https://doi.org/10.1136/jmg.2009.072082.
Calakos N, Patel VD, Gottron M, Wang G, Tran-Viet K-N, Brewington D, et al. Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia. J Med Genet. 2010 Sep;47(9):646–50.
Calakos, Nicole, et al. “Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia.J Med Genet, vol. 47, no. 9, Sept. 2010, pp. 646–50. Pubmed, doi:10.1136/jmg.2009.072082.
Calakos N, Patel VD, Gottron M, Wang G, Tran-Viet K-N, Brewington D, Beyer JL, Steffens DC, Krishnan RR, Züchner S. Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia. J Med Genet. 2010 Sep;47(9):646–650.

Published In

J Med Genet

DOI

EISSN

1468-6244

Publication Date

September 2010

Volume

47

Issue

9

Start / End Page

646 / 650

Location

England

Related Subject Headings

  • Mutation
  • Molecular Sequence Data
  • Molecular Chaperones
  • Middle Aged
  • Inclusion Bodies
  • Humans
  • Genetics & Heredity
  • Dystonic Disorders
  • Cell Line
  • Amino Acid Substitution