Investigators at University of Tennessee publish new data on dystonia
2009 JUN 2 - (NewsRx.com) -- "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 Delta GAG mutation carriers present with late-onset focal dystonia," researchers in the United States report. "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 Delta GAG DYT1 dystonia and 88 subjects with Delta GAG-negative dystonia. HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A Delta GAG 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 Delta GAG 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," wrote J. Xiao and colleagues, University of Tennessee. The researchers concluded: "Second, Exon 5 mutations in TOR1A are rarely associated with non-generalized primary dystonia." Xiao and colleagues published their study in BMC Medical Genetics (High-throughput mutational analysis of TOR1A in primary dystonia. BMC Medical Genetics, 2009;10():24). For additional information, contact J. Xiao, University of Tennessee, Center Health Science, Dept. of Neurology, Memphis, TN 38163, USA. Publisher contact information for the journal BMC Medical Genetics is: Biomedical Central Ltd., Current Science Group, Middlesex House, 34-42 Cleveland St., London W1T 4LB, England. Keywords: United States, Memphis, Blepharospasm, Dystonia, Ophthalmology, Spasmodic Dysphonia, Torticollis, Voice Disorders, University of Tennessee. This article was prepared by Life Science Weekly editors from staff and other reports. Copyright 2009, Life Science Weekly via NewsRx.com.
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