Spinocerebellar Ataxia Type 12

Susan Elizabeth Holmes, Elizabeth O'Hearn, Natividad Cortez-Apreza, H. S. Hwang, Christopher A. Ross, S. Strack, Russell L. Margolis

Research output: Chapter in Book/Report/Conference proceedingChapter

6 Scopus citations


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 (B?1) of the B? regulatory subunit. Repeat expansion appears to drive increased transcription from this promoter, suggesting that disease pathogenesis may involve overexpression of B?1 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 B? isoforms, including B?2, 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 B?2.

Original languageEnglish (US)
Title of host publicationGenetic Instabilities and Neurological Diseases
Number of pages13
ISBN (Print)9780123694621
StatePublished - Jul 11 2006

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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