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

The endophenotype and the phenotype: temporal discrimination and adult-onset dystonia.

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  • 1Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland; University College Dublin, Dublin, Ireland.

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.

© 2013 International Parkinson and Movement Disorder Society.

KEYWORDS:

focal dystonia; mediational endophenotype; phenotype; putamen; temporal discrimination

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