Temporal discrimination threshold: VBM evidence for an endophenotype in adult onset primary torsion dystonia.

Hdl Handle:
http://hdl.handle.net/10147/207702
Title:
Temporal discrimination threshold: VBM evidence for an endophenotype in adult onset primary torsion dystonia.
Authors:
Bradley, D; Whelan, R; Walsh, R; Reilly, R B; Hutchinson, S; Molloy, F; Hutchinson, M
Affiliation:
Department of Neurology, St Vincent's University Hospital, Dublin, Ireland., david.bradley@ucd.ie
Citation:
Brain. 2009 Sep;132(Pt 9):2327-35. Epub 2009 Jun 12.
Journal:
Brain : a journal of neurology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207702
DOI:
10.1093/brain/awp156
PubMed ID:
19525326
Abstract:
Familial adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance. Most adult-onset primary torsion dystonia patients are sporadic cases. Disordered sensory processing is found in adult-onset primary torsion dystonia patients; if also present in their unaffected relatives this abnormality may indicate non-manifesting gene carriage. Temporal discrimination thresholds (TDTs) are abnormal in adult-onset primary torsion dystonia, but their utility as a possible endophenotype has not been examined. We examined 35 adult-onset primary torsion dystonia patients (17 familial, 18 sporadic), 42 unaffected first-degree relatives of both familial and sporadic adult-onset primary torsion dystonia patients, 32 unaffected second-degree relatives of familial adult-onset primary torsion dystonia (AOPTD) patients and 43 control subjects. TDT was measured using visual and tactile stimuli. In 33 unaffected relatives, voxel-based morphometry was used to compare putaminal volumes between relatives with abnormal and normal TDTs. The mean TDT in 26 control subjects under 50 years of age was 22.85 ms (SD 8.00; 95% CI: 19.62-26.09 ms). The mean TDT in 17 control subjects over 50 years was 30.87 ms (SD 5.48; 95% CI: 28.05-33.69 ms). The upper limit of normal, defined as control mean + 2.5 SD, was 42.86 ms in the under 50 years group and 44.58 ms in the over 50 years group. Thirty out of thirty-five (86%) AOPTD patients had abnormal TDTs with similar frequencies of abnormalities in sporadic and familial patients. Twenty-two out of forty-two (52%) unaffected first-degree relatives had abnormal TDTs with similar frequencies in relatives of sporadic and familial AOPTD patients. Abnormal TDTs were found in 16/32 (50%) of second-degree relatives. Voxel-based morphometry analysis comparing 13 unaffected relatives with abnormal TDTs and 20 with normal TDTs demonstrated a bilateral increase in putaminal grey matter in unaffected relatives with abnormal TDTs. The prevalence of abnormal TDTs in sporadic and familial AOPTD patients and their first-degree relatives follows the rules for a useful endophenotype. A structural correlate of abnormal TDTs in unaffected first-degree relatives was demonstrated using voxel-based morphometry. Voxel-based morphometry findings indicate that putaminal enlargement in AOPTD is a primary phenomenon. TDTs may be an effective tool in AOPTD research with particular relevance to genetic studies of the disorder.
Language:
eng
MeSH:
Adult; Aged; *Discrimination (Psychology); Dystonia Musculorum Deformans/pathology/*psychology; Heterozygote; Humans; Magnetic Resonance Imaging/methods; Middle Aged; Pedigree; Phenotype; Putamen/pathology; Sensory Thresholds; *Time Perception; Young Adult
ISSN:
1460-2156 (Electronic); 0006-8950 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorBradley, Den_GB
dc.contributor.authorWhelan, Ren_GB
dc.contributor.authorWalsh, Ren_GB
dc.contributor.authorReilly, R Ben_GB
dc.contributor.authorHutchinson, Sen_GB
dc.contributor.authorMolloy, Fen_GB
dc.contributor.authorHutchinson, Men_GB
dc.date.accessioned2012-02-01T10:35:23Z-
dc.date.available2012-02-01T10:35:23Z-
dc.date.issued2012-02-01T10:35:23Z-
dc.identifier.citationBrain. 2009 Sep;132(Pt 9):2327-35. Epub 2009 Jun 12.en_GB
dc.identifier.issn1460-2156 (Electronic)en_GB
dc.identifier.issn0006-8950 (Linking)en_GB
dc.identifier.pmid19525326en_GB
dc.identifier.doi10.1093/brain/awp156en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207702-
dc.description.abstractFamilial adult-onset primary torsion dystonia is an autosomal dominant disorder with markedly reduced penetrance. Most adult-onset primary torsion dystonia patients are sporadic cases. Disordered sensory processing is found in adult-onset primary torsion dystonia patients; if also present in their unaffected relatives this abnormality may indicate non-manifesting gene carriage. Temporal discrimination thresholds (TDTs) are abnormal in adult-onset primary torsion dystonia, but their utility as a possible endophenotype has not been examined. We examined 35 adult-onset primary torsion dystonia patients (17 familial, 18 sporadic), 42 unaffected first-degree relatives of both familial and sporadic adult-onset primary torsion dystonia patients, 32 unaffected second-degree relatives of familial adult-onset primary torsion dystonia (AOPTD) patients and 43 control subjects. TDT was measured using visual and tactile stimuli. In 33 unaffected relatives, voxel-based morphometry was used to compare putaminal volumes between relatives with abnormal and normal TDTs. The mean TDT in 26 control subjects under 50 years of age was 22.85 ms (SD 8.00; 95% CI: 19.62-26.09 ms). The mean TDT in 17 control subjects over 50 years was 30.87 ms (SD 5.48; 95% CI: 28.05-33.69 ms). The upper limit of normal, defined as control mean + 2.5 SD, was 42.86 ms in the under 50 years group and 44.58 ms in the over 50 years group. Thirty out of thirty-five (86%) AOPTD patients had abnormal TDTs with similar frequencies of abnormalities in sporadic and familial patients. Twenty-two out of forty-two (52%) unaffected first-degree relatives had abnormal TDTs with similar frequencies in relatives of sporadic and familial AOPTD patients. Abnormal TDTs were found in 16/32 (50%) of second-degree relatives. Voxel-based morphometry analysis comparing 13 unaffected relatives with abnormal TDTs and 20 with normal TDTs demonstrated a bilateral increase in putaminal grey matter in unaffected relatives with abnormal TDTs. The prevalence of abnormal TDTs in sporadic and familial AOPTD patients and their first-degree relatives follows the rules for a useful endophenotype. A structural correlate of abnormal TDTs in unaffected first-degree relatives was demonstrated using voxel-based morphometry. Voxel-based morphometry findings indicate that putaminal enlargement in AOPTD is a primary phenomenon. TDTs may be an effective tool in AOPTD research with particular relevance to genetic studies of the disorder.en_GB
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.mesh*Discrimination (Psychology)en_GB
dc.subject.meshDystonia Musculorum Deformans/pathology/*psychologyen_GB
dc.subject.meshHeterozygoteen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMagnetic Resonance Imaging/methodsen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshPedigreeen_GB
dc.subject.meshPhenotypeen_GB
dc.subject.meshPutamen/pathologyen_GB
dc.subject.meshSensory Thresholdsen_GB
dc.subject.mesh*Time Perceptionen_GB
dc.subject.meshYoung Adulten_GB
dc.titleTemporal discrimination threshold: VBM evidence for an endophenotype in adult onset primary torsion dystonia.en_GB
dc.contributor.departmentDepartment of Neurology, St Vincent's University Hospital, Dublin, Ireland., david.bradley@ucd.ieen_GB
dc.identifier.journalBrain : a journal of neurologyen_GB
dc.description.provinceLeinster-

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