The endophenotype and the phenotype: temporal discrimination and adult-onset dystonia.
Mov Disord
; 28(13): 1766-74, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-24108447
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Discriminação Psicológica
/
Distonia
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article