A duplication at chromosome 11q12.2–11q12.3 is associated with spinocerebellar ataxia type 20

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 withi...

Full description

Saved in:
Bibliographic Details
Published in:Human molecular genetics 2008-12, Vol.17 (24), p.3847-3853
Main Authors: Knight, Melanie A., Hernandez, Dena, Diede, Scott J., Dauwerse, Hans G., Rafferty, Ian, van de Leemput, Joyce, Forrest, Susan M., Gardner, R.J.McKinlay, Storey, Elsdon, van Ommen, Gert-Jan B., Tapscott, Stephen J., Fischbeck, Kenneth H., Singleton, Andrew B.
Format: Article
Language:English
Subjects:
Chromosome Mapping
Chromosomes, Human, Pair 11 - genetics
Female
Gene Duplication
Genetic Linkage
Humans
Male
Multigene Family - genetics
Oligonucleotide Array Sequence Analysis
Pedigree
Polymorphism, Single Nucleotide
Reverse Transcriptase Polymerase Chain Reaction
Spinocerebellar Ataxias - classification
Spinocerebellar Ataxias - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/ddn283