An examination of TOR1A variants in recurrent major depression.
ABSTRACT Observations of comorbid depression in subjects with primary dystonia have suggested a dual role for the TOR1A gene in mood disorders and movement disorders. We conducted a systematic search for carriers of the ΔGAG deletion and for other variants in TOR1A exon 5 among 414 Caucasian subjects with recurrent major depression from the Upper Palatinate.
Allele frequencies were determined for 27 TOR1A diallelic markers, including two novel synonymous substitutions (L262L and E310E) in the region encoding the torsinA C-terminus, plus four novel variants in the gene's 3'UTR. No carriers of the ΔGAG deletion were observed. When data were compared to previously examined control populations, no significant allelic associations were noted after corrections for multiple testing.
The present study adds to the spectrum of TOR1A mutations but provides no evidence of a common genetic predisposition to DYT1 dystonia and recurrent major depression.
Article: Torticollis under cyclobenzaprine.[Show abstract] [Hide abstract]
ABSTRACT: The muscle-relaxing 5-HT(2) receptor antagonist cyclobenzaprine is structurally closely related to amitriptyline. It is widely used to treat patients presenting with back pain and fibromyalgia. Very rarely cyclobenzaprine toxicity can result in extrapyramidal symptoms, but occurrence of torticollis has not been reported so far. We report on a patient presenting with torticollis and myoclonic movements after treatment with cyclobenzaprine, who was successfully treated with intravenous biperiden. This case might be additional evidence for the necessity of appropriate dosage in case of liver impairment. Secondly there are possibly consequences as regards the therapy of motor side effects.Pharmacology 08/2009; 84(2):91-2. DOI:10.1159/000227773 · 1.58 Impact Factor
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ABSTRACT: Although the c.904_906delGAG mutation in Exon 5 of TOR1A typically manifests as early-onset generalized dystonia, DYT1 dystonia is genetically and clinically heterogeneous. Recently, another Exon 5 mutation (c.863G>A) has been associated with early-onset generalized dystonia and some DeltaGAG mutation carriers present with late-onset focal dystonia. The aim of this study was to identify TOR1A Exon 5 mutations in a large cohort of subjects with mainly non-generalized primary dystonia. High resolution melting (HRM) was used to examine the entire TOR1A Exon 5 coding sequence in 1014 subjects with primary dystonia (422 spasmodic dysphonia, 285 cervical dystonia, 67 blepharospasm, 41 writer's cramp, 16 oromandibular dystonia, 38 other primary focal dystonia, 112 segmental dystonia, 16 multifocal dystonia, and 17 generalized dystonia) and 250 controls (150 neurologically normal and 100 with other movement disorders). Diagnostic sensitivity and specificity were evaluated in an additional 8 subjects with known DeltaGAG DYT1 dystonia and 88 subjects with DeltaGAG-negative dystonia. HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A DeltaGAG and c.863G>A mutations. Melting curves were normal in 250/250 controls and 1012/1014 subjects with primary dystonia. The two subjects with shifted melting curves were found to harbor the classic DeltaGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset multifocal dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia. First, HRM is an inexpensive, diagnostically sensitive and specific, high-throughput method for mutation discovery. Second, Exon 5 mutations in TOR1A are rarely associated with non-generalized primary dystonia.BMC Medical Genetics 02/2009; 10:24. DOI:10.1186/1471-2350-10-24 · 2.45 Impact Factor
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ABSTRACT: Cervical dystonia (CD) or spasmodic torticollis is the most frequent form of focal dystonia. Cervical dystonia is characterized by sustained neck spasms, abnormal head posture, head tremor, and pain. A 53-year-old male patient with the diagnosis of CD developed an episode of delusional depression and was treated with electroconvulsive therapy (ECT). An unexpected and dramatic improvement of CD was seen during the first 2 days after each ECT session. That therapeutic effect was not sustained and vanished soon afterward. The effectiveness of ECT for CD, although too brief to be recommended as a useful treatment, may shed light on the pathophysiology of this problematic movement disorder.The journal of ECT 02/2009; 25(2):135-6. DOI:10.1097/YCT.0b013e31818b0ab1 · 1.39 Impact Factor