INTRODUCTION This proposal is for core support for the projects of this grant application directed towards elucidation of the molecular etiology and pathophysiology of early onset torsion dystonia and for establishment/conversion of this clinical core into an international resource for dystonia-related investigations. Centralized core services are critical to the stability and functioning of each of the specific projects and indispensable to the coordinated and efficient attainment of the overall project goals. The functions of this core include patient recruitment, enrollment and phenotypic characterization, human tissue collection/cell line establishment and genotype analysis, and database maintenance and expansion. To ensure that this information is most readily available to colleagues across the nation, we will establish a web-based database, containing deidentified information, on all dystonia subjects who participate In research studies and consented to share their Information with investigators worldwide. To ensure that the privacy of those with familial dystonia is protected, de-identified clinical Information about the proband only will be entered in the web-based database. Further details regarding subject identity protection are in the Research Design and Methods section. This information and access to patient/family samples will allow other groups to move forward with research in human dystonia. Included as part of this core are two human pilot studies designed to explore the role of the TOR1A gene and the mutant torsinA protein in the development of dystonia. Should positive results be obtained in either of these pilot studies, they may be expanded in the future. In addition, these wellcharacterized patients and materials will be available for future clinical trials and molecular genetic studies as they are developed based on new Insights gained in the various projects described in this center grant.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center (P50)
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Special Emphasis Panel (ZNS1-SRB-B)
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Massachusetts General Hospital
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Cho, Jin A; Zhang, Xuan; Miller, Gregory M et al. (2014) 4-Phenylbutyrate attenuates the ER stress response and cyclic AMP accumulation in DYT1 dystonia cell models. PLoS One 9:e110086
Bragg, D Cristopher; Sharma, Nutan (2014) Update on treatments for dystonia. Curr Neurol Neurosci Rep 14:454
Nery, Flavia C; da Hora, Cintia C; Atai, Nadia A et al. (2014) Microfluidic platform to evaluate migration of cells from patients with DYT1 dystonia. J Neurosci Methods 232:181-8
Saunders-Pullman, Rachel; Fuchs, Tania; San Luciano, Marta et al. (2014) Heterogeneity in primary dystonia: lessons from THAP1, GNAL, and TOR1A in Amish-Mennonites. Mov Disord 29:812-8
Hettich, Jasmin; Ryan, Scott D; de Souza, Osmar Norberto et al. (2014) Biochemical and cellular analysis of human variants of the DYT1 dystonia protein, TorsinA/TOR1A. Hum Mutat 35:1101-13
Oleas, Janneth; Yokoi, Fumiaki; DeAndrade, Mark P et al. (2013) Engineering animal models of dystonia. Mov Disord 28:990-1000
Fuchs, Tania; Saunders-Pullman, Rachel; Masuho, Ikuo et al. (2013) Mutations in GNAL cause primary torsion dystonia. Nat Genet 45:88-92
Mizrak, Arda; Bolukbasi, Mehmet Fatih; Ozdener, Gokhan Baris et al. (2013) Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth. Mol Ther 21:101-8
Armata, Ioanna A; Balaj, Leonora; Kuster, John K et al. (2013) Dopa-responsive dystonia: functional analysis of single nucleotide substitutions within the 5' untranslated GCH1 region. PLoS One 8:e76975
Waugh, Jeffrey L; Sharma, Nutan (2013) Clinical neurogenetics: dystonia from phenotype to genotype. Neurol Clin 31:969-86

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