title: A duplication at chromosome 11q12.2-11q12.3 is associated with spinocerebellar ataxia type 20.
abstract: 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.
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20894-3708, USA. knightme@mail.nih.gov
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Knight
authors.forename: Dena
authors.initials: D
authors.lastname: Hernandez
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Diede
authors.forename: Hans G
authors.initials: HG
authors.lastname: Dauwerse
authors.forename: Ian
authors.initials: I
authors.lastname: Rafferty
authors.forename: Joyce
authors.initials: J
authors.lastname: van de Leemput
authors.forename: Susan M
authors.initials: SM
authors.lastname: Forrest
authors.forename: R J McKinlay
authors.initials: RJ
authors.lastname: Gardner
authors.forename: Elsdon
authors.initials: E
authors.lastname: Storey
authors.forename: Gert-Jan B
authors.initials: GJ
authors.lastname: van Ommen
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Tapscott
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Fischbeck
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
mesh_terms: D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D005810:Multigene Family / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020754:Spinocerebellar Ataxias / Q000145:classification* / Q000235:genetics*
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