Background: TOR1A encodes a chaperone-like AAA-ATPase whose ΔGAG (ΔE) mutation is responsible for an early-onset, generalized dystonia syndrome. Because of the established role of the TOR1A gene in heritable generalized 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: We have identified a novel, rare TOR1A variant in an individual with late-onset, focal dystonia and provided evidence 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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