Hutchinson M1,2, Kimmich O1,2, Molloy A1,2, Whelan R3,4, Molloy F5, Lynch T6, Healy DG7, Walsh C8, Edwards MJ9, Ozelius O10, Reilly RB3, O’Riordan S1,2

 

Mov Disord. 2013 Nov;28(13):1766-74. doi: 10.1002/mds.25676. Epub 2013 Oct 9.

 

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 ABSTRACT:


 

The pathogenesis and the genetic basis of adult-onset primary torsion dystonia remain poorly understood. Because of markedly reduced penetrance in this disorder, a number of endophenotypes have been proposed; many of these may be epiphenomena secondary to disease manifestation. Mediational endophenotypes represent gene expression; the study of trait (endophenotypic) rather than state (phenotypic) characteristics avoids the misattribution of secondary adaptive cerebral changes to pathogenesis. We argue that abnormal temporal discrimination is a mediational endophenotype; its use facilitates examination of the effects of age, gender, and environment on disease penetrance in adult-onset dystonia. Using abnormal temporal discrimination in unaffected first-degree relatives as a marker for gene mutation carriage may inform exome sequencing techniques in families with few affected individuals. We further hypothesize that abnormal temporal discrimination reflects dysfunction in an evolutionarily conserved subcortical-basal ganglia circuit for the detection of salient novel environmental change. The mechanisms of dysfunction in this pathway should be a focus for future research in the pathogenesis of adult-onset primary torsion dystonia.

 


 

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Copyright © 2013 International Parkinson and Movement Disorder Society.