The Experts below are selected from a list of 213 Experts worldwide ranked by ideXlab platform
Zbigniew K Wszolek - One of the best experts on this subject based on the ideXlab platform.
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High-throughput mutational analysis of TOR1A in primary Dystonia
BMC Medical Genetics, 2009Co-Authors: Jianfeng Xiao, Robert W Bastian, Joel S Perlmutter, Brad A Racette, Samer D Tabbal, Morvarid Karimi, Randal C Paniello, Andrew Blitzer, Sat Dev Batish, Zbigniew K WszolekAbstract:Background 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 ΔGAG 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. Methods 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 ΔGAG DYT1 Dystonia and 88 subjects with ΔGAG-negative Dystonia. Results HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG 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 ΔGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset Multifocal Dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia. Conclusion 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.
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High-throughput mutational analysis of TOR1A in primary Dystonia
BMC Medical Genetics, 2009Co-Authors: Jianfeng Xiao, Robert W Bastian, Joel S Perlmutter, Brad A Racette, Samer D Tabbal, Morvarid Karimi, Randal C Paniello, Andrew Blitzer, Sat Dev Batish, Zbigniew K WszolekAbstract: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 ΔGAG 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 ΔGAG DYT1 Dystonia and 88 subjects with ΔGAG-negative Dystonia. HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG 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 ΔGAG 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.
Jianfeng Xiao - One of the best experts on this subject based on the ideXlab platform.
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High-throughput mutational analysis of TOR1A in primary Dystonia
BMC Medical Genetics, 2009Co-Authors: Jianfeng Xiao, Robert W Bastian, Joel S Perlmutter, Brad A Racette, Samer D Tabbal, Morvarid Karimi, Randal C Paniello, Andrew Blitzer, Sat Dev Batish, Zbigniew K WszolekAbstract:Background 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 ΔGAG 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. Methods 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 ΔGAG DYT1 Dystonia and 88 subjects with ΔGAG-negative Dystonia. Results HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG 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 ΔGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset Multifocal Dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia. Conclusion 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.
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High-throughput mutational analysis of TOR1A in primary Dystonia
BMC Medical Genetics, 2009Co-Authors: Jianfeng Xiao, Robert W Bastian, Joel S Perlmutter, Brad A Racette, Samer D Tabbal, Morvarid Karimi, Randal C Paniello, Andrew Blitzer, Sat Dev Batish, Zbigniew K WszolekAbstract: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 ΔGAG 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 ΔGAG DYT1 Dystonia and 88 subjects with ΔGAG-negative Dystonia. HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG 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 ΔGAG 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.
Vladimir S. Kostić - One of the best experts on this subject based on the ideXlab platform.
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Intrafamilial phenotypic and genetic heterogeneity of Dystonia.
Journal of the Neurological Sciences, 2006Co-Authors: Vladimir S. Kostić, Marina Svetel, K. Kabakci, Aleksandar J. Ristić, Igor Petrovic, Birgitt Schüle, Norman Kock, Ana Djarmati, Stanka Romac, Christine KleinAbstract:Most cases of early-onset primary torsion Dystonia are caused by the same 3-bp (GAG) deletion in the DYT1 gene. We describe a large Serbian family with significant intrafamilial variability of the DYT1 phenotype, from asymptomatic carrier status to late-onset focal, and generalized jerky Dystonia. Seven mutation carriers (six proven by direct analysis and one by inferred haplotype) were identified, but only two of them were affected by Dystonia (penetrance reduced to 29%). In addition, three GAG-deletion-negative family members also developed Dystonia (two Multifocal Dystonia and one torticollis), suggesting that their involuntary movements are due to some other etiological factor(s) (i.e., another Dystonia gene), or may be psychogenic.
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DYT1 mutation in primary torsion Dystonia in a Serbian population
Journal of Neurology, 2001Co-Authors: Tamara Major, Stanka Romac, Marina Svetel, Vladimir S. KostićAbstract:Primary torsion Dystonia (PTD) is a clinically and genetically heterogeneous movement disorder. A GAG deletion at position 946 in the DYT1 gene is responsible for most cases of autosomal dominant early-onset PTD. We analysed the DYT1 mutation in 50 patients from a Serbian population, selected according to the proposed guidelines for diagnostic testing: (a) 38 patients with PTD onset < 26 years, and (b) 12 patients with the disease onset ± 26 years, but with at least one affected family member with early-onset Dystonia. Only three apparently sporadic patients among the 50 individuals tested were positive for the GAG deletion in the DYT1 gene: one with typical, generalized, one with long-lasting, non-progressive segmental, and one with Multifocal Dystonia. Molecular analysis of relatives in 2 families revealed that the lack of family history was due to reduced penetrance.
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Dystonia in Wilson's disease
Movement Disorders, 2001Co-Authors: Marina Svetel, Dusko Kozic, Elka Stefanova, Robert Semnic, Natasa Dragasevic, Vladimir S. KostićAbstract:The frequency and type of dystonic movements, as well as brain abnormalities, as depicted with magnetic resonance imaging (MRI), which might correlate with Dystonia, were studied in 27 consecutive patients with a neurologic form of Wilson's disease (WD) and optimized treatment. Dystonia was found in 10 patients (37%), being generalized in half of them, while two patients had segmental, two patients Multifocal Dystonia, and one patient bilateral foot Dystonia. Dystonia was a presenting sign in four patients and developed later in the course of the disease in six patients, despite the administered therapy for WD. Putamen was the only structure significantly more frequently lesioned in dystonic (80%) in comparison to WD patients without Dystonia (24%), suggesting a relation between abnormalities in this brain region and dystonic movements in WD.
Robert W Bastian - One of the best experts on this subject based on the ideXlab platform.
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High-throughput mutational analysis of TOR1A in primary Dystonia
BMC Medical Genetics, 2009Co-Authors: Jianfeng Xiao, Robert W Bastian, Joel S Perlmutter, Brad A Racette, Samer D Tabbal, Morvarid Karimi, Randal C Paniello, Andrew Blitzer, Sat Dev Batish, Zbigniew K WszolekAbstract:Background 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 ΔGAG 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. Methods 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 ΔGAG DYT1 Dystonia and 88 subjects with ΔGAG-negative Dystonia. Results HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG 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 ΔGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset Multifocal Dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia. Conclusion 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.
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High-throughput mutational analysis of TOR1A in primary Dystonia
BMC Medical Genetics, 2009Co-Authors: Jianfeng Xiao, Robert W Bastian, Joel S Perlmutter, Brad A Racette, Samer D Tabbal, Morvarid Karimi, Randal C Paniello, Andrew Blitzer, Sat Dev Batish, Zbigniew K WszolekAbstract: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 ΔGAG 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 ΔGAG DYT1 Dystonia and 88 subjects with ΔGAG-negative Dystonia. HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG 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 ΔGAG 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.
Joel S Perlmutter - One of the best experts on this subject based on the ideXlab platform.
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High-throughput mutational analysis of TOR1A in primary Dystonia
BMC Medical Genetics, 2009Co-Authors: Jianfeng Xiao, Robert W Bastian, Joel S Perlmutter, Brad A Racette, Samer D Tabbal, Morvarid Karimi, Randal C Paniello, Andrew Blitzer, Sat Dev Batish, Zbigniew K WszolekAbstract:Background 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 ΔGAG 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. Methods 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 ΔGAG DYT1 Dystonia and 88 subjects with ΔGAG-negative Dystonia. Results HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG 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 ΔGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset Multifocal Dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia. Conclusion 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.
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High-throughput mutational analysis of TOR1A in primary Dystonia
BMC Medical Genetics, 2009Co-Authors: Jianfeng Xiao, Robert W Bastian, Joel S Perlmutter, Brad A Racette, Samer D Tabbal, Morvarid Karimi, Randal C Paniello, Andrew Blitzer, Sat Dev Batish, Zbigniew K WszolekAbstract: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 ΔGAG 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 ΔGAG DYT1 Dystonia and 88 subjects with ΔGAG-negative Dystonia. HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG 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 ΔGAG 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.