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

Nicole Calakos, Viren D. Patel, Melissa Gottron, Gaofeng Wang, Khan Nhat Tran-Viet, Danielle Brewington, John L. Beyer, David C. Steffens, Ranga R. Krishnan, Stephan L Zuchner

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Background: TOR1A encodes a chaperone-like AAA-ATPase whose ΔGAG (ΔE) 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 ΔE, 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.

Original languageEnglish
Pages (from-to)646-650
Number of pages5
JournalJournal of Medical Genetics
Volume47
Issue number9
DOIs
StatePublished - Sep 1 2010

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Dystonic Disorders
Dystonia
Mutation
Adenosine Triphosphatases
Missense Mutation
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia. / Calakos, Nicole; Patel, Viren D.; Gottron, Melissa; Wang, Gaofeng; Tran-Viet, Khan Nhat; Brewington, Danielle; Beyer, John L.; Steffens, David C.; Krishnan, Ranga R.; Zuchner, Stephan L.

In: Journal of Medical Genetics, Vol. 47, No. 9, 01.09.2010, p. 646-650.

Research output: Contribution to journalArticle

Calakos, N, Patel, VD, Gottron, M, Wang, G, Tran-Viet, KN, Brewington, D, Beyer, JL, Steffens, DC, Krishnan, RR & Zuchner, SL 2010, 'Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia', Journal of Medical Genetics, vol. 47, no. 9, pp. 646-650. https://doi.org/10.1136/jmg.2009.072082
Calakos, Nicole ; Patel, Viren D. ; Gottron, Melissa ; Wang, Gaofeng ; Tran-Viet, Khan Nhat ; Brewington, Danielle ; Beyer, John L. ; Steffens, David C. ; Krishnan, Ranga R. ; Zuchner, Stephan L. / Functional evidence implicating a novel TOR1A mutation in idiopathic, late-onset focal dystonia. In: Journal of Medical Genetics. 2010 ; Vol. 47, No. 9. pp. 646-650.
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