Large deletions account for an increasing number of mutations in SGCE |
| |
| Authors: | Fabin Han MD MSc Lemuel Racacho BSc Howard Yang Tara Read BSc Oksana Suchowersky MD Anthony E. Lang MD David A. Grimes MD Dennis E. Bulman PhD |
| |
| Affiliation: | 1. Ottawa Health Research Institute, Ottawa, Ontario, Canada;2. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada;3. Center for Neuromuscular Research, University of Ottawa, Ottawa, Ontario, Canada;4. Department of Medical Genetics, University of Calgary, Hotchkiss Brain Institute, Calgary, Alberta, Canada;5. Department of Clinical Neurosciences, Hotchkiss Brain Institute, Calgary, Alberta, Canada;6. Division of Neurology, Department of Medicine, University Health Network, Toronto Western Hospital, Ontario, Canada;7. Department of Medicine, Division of Neurology, University of Ottawa, Ottawa, Ontario, Canada |
| |
| Abstract: | Myoclonus‐dystonia (M‐D) (MIM 159900) is a rare “dystonia plus” syndrome, characterized by rapid myoclonic jerks, predominantly in the neck and upper limbs, in combination with dystonia. Mutations in the gene ε‐sarcoglycan (SGCE) are known to be responsible for approximately one‐third of cases. We screened 21 probands diagnosed with M‐D for large deletions who were mutation negative as determined by PCR‐direct sequencing. Multiplex PCR and quantification of PCR products was performed using a modified application of denaturing high performance liquid chromatography (dHPLC). We have identified two novel large multiexonic deletions of SGCE, which were confirmed by amplifying and sequencing the deletion breakpoints. Five other families were found to harbor small mutations identified by direct sequencing. Analysis of the region surrounding the deletions demonstrates that both deletions are the result of nonhomologous recombination with homologous end joining. This is only the second report of intragenic deletions with SGCE and it highlights the need to include exonic copy number variation when performing mutational analysis of SGCE. © 2007 Movement Disorder Society |
| |
| Keywords: | myoclonus dystonia ε ‐sarcoglycan SGCE deletions |
|
|
