Book chapter
Chapter 31 - Spinocerebellar Ataxia Type 12
Genetic Instabilities and Neurological Diseases, Second Edition, pp.461-473
Elsevier Inc, Second Edition
2006
DOI: 10.1016/B978-012369462-1/50032-6
Abstract
This chapter focuses on spinocerebellar ataxia type 12 (SCA12) caused by a CAG repeat expansion in PPP2R2 that encodes one of the brain-specific regulatory subunits of the trimeric phosphatase PP2A. SCA12 is the second most common SCA in India, accounting for approximately 8% of dominant ataxia cases; however, it is a rare disease in all other populations studied to date, having been found in only the single North American index pedigree. Clinically, SCA12 is the only inherited SCA that has action tremor as the presenting and most common sign. The SCA12 CAG repeat is found in the probable promoter region of the PPP2R2B variant encoding the predominant isoform (Bβ1) of the Bβ regulatory subunit. Repeat expansion appears to drive increased transcription from this promoter, suggesting that disease pathogenesis may involve overexpression of Bβ1 and lead to altered activity of PP2A, a ubiquitous enzyme implicated in multiple cellular processes including apoptosis. The SCA12 repeat is also within the intronic sequence of multiple alternately spliced transcripts with alternate promoters that encode additional Bβ isoforms, including Bβ2, which targets PP2A to the mitochondria, and promotes apoptosis when overexpressed. Pathogenesis may also involve an expansion-induced shift in splicing or choice of promoters, leading to an increase in expression of Bβ2.
Details
- Title: Subtitle
- Chapter 31 - Spinocerebellar Ataxia Type 12
- Creators
- Susan E Holmes - Laboratory of Genetic Neurobiology, Division of Neurobiology, Department of Psychiatry Johns Hopkins University School of Medicine, Baltimore, MarylandElizabeth O'Hearn - Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MarylandNatividad Cortez-Apreza - Laboratory of Genetic Neurobiology, Division of Neurobiology, Department of Psychiatry Johns Hopkins University School of Medicine, Baltimore, MarylandH.S Hwang - Laboratory of Genetic Neurobiology, Division of Neurobiology, Department of Psychiatry Johns Hopkins University School of Medicine, Baltimore, MarylandChristopher A Ross - Laboratory of Genetic Neurobiology, Division of Neurobiology, Department of Psychiatry Johns Hopkins University School of Medicine, Baltimore, MarylandS Strack - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IowaRussell L Margolis - Laboratory of Genetic Neurobiology, Division of Neurobiology, Department of Psychiatry Johns Hopkins University School of Medicine, Baltimore, Maryland
- Resource Type
- Book chapter
- Publication Details
- Genetic Instabilities and Neurological Diseases, Second Edition, pp.461-473
- Edition
- Second Edition
- DOI
- 10.1016/B978-012369462-1/50032-6
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 2006
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984068259102771
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