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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
High-throughput mutational analysis of TOR1A in primary dystonia
BMC Medical Genetics, Volume 10, Article 24, Year 2009
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Description
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. © 2009 Xiao et al; licensee BioMed Central Ltd.
Authors & Co-Authors
Bastian, Robert W.
Unknown Affiliation
Perlmutter, Joel S.
United States, St. Louis
Washington University School of Medicine in St. Louis
Racette, Brad A.
United States, St. Louis
Washington University School of Medicine in St. Louis
Tabbal, Samer D.
United States, St. Louis
Washington University School of Medicine in St. Louis
Wszołek, Zbigniew K.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Uitti, Ryan J.
United States, Jacksonville
Mayo Clinic in Jacksonville, Florida
Statistics
Citations: 27
Authors: 6
Affiliations: 6
Identifiers
Doi:
10.1186/1471-2350-10-24
ISSN:
14712350
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health
Study Design
Cohort Study
Participants Gender
Female