Human Molecular Genetics Advance Access originally published online on September 18, 2008
Human Molecular Genetics 2008 17(24):3847-3853; doi:10.1093/hmg/ddn283
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A duplication at chromosome 11q12.2–11q12.3 is associated with spinocerebellar ataxia type 20
1 Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA 2 Molecular Genetics Unit, National Institute in Aging, National Institutes of Health, Bethesda, MD, USA, 3 Department of Pediatrics, University of Washington, Seattle, WA, USA, 4 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA, 5 Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands, 6 Australian Genome Research Facility, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia, 7 Genetic Health Services Victoria, Melbourne, Australia, 8 Murdoch Childrens Research Institute, Royal Children’s Hospital, Melbourne, Australia 9 Department of Medicine (Neurosciences), Alfred Hospital Campus of Monash University, Melbourne, Australia
* To whom correspondence should be addressed at: Medical Genetics Branch, Section on Molecular Neurogenetics, National Human Genome Research Institute, National Institutes of Health, Building 35, Room 1A105, 35 Convent Drive, MSC 3708, Bethesda, MD 20894-3708, USA. Tel: +1 3014510902; Fax: +1 3014026438; Email: knightme{at}mail.nih.gov and Melanie_A_Knight{at}hotmail.com.
Received June 26, 2008; Accepted September 2, 2008
Spinocerebellar ataxia type 20 (SCA20) has been linked to chromosome 11q12, but the underlying genetic defect has yet to be identified. We applied single-nucleotide polymorphism genotyping to detect structural alterations in the genomic DNA of patients with SCA20. We found a 260 kb duplication within the previously linked SCA20 region, which was confirmed by quantitative polymerase chain reaction and fiber fluorescence in situ hybridization, the latter also showing its direct orientation. The duplication spans 10 known and 2 unknown genes, and is present in all affected individuals in the single reported SCA20 pedigree. While the mechanism whereby this duplication may be pathogenic remains to be established, we speculate that the critical gene within the duplicated segment may be DAGLA, the product of which is normally present at the base of Purkinje cell dendritic spines and contributes to the modulation of parallel fiber-Purkinje cell synapses.