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Updated: May 30, 2026
08:51
Cerebellar Regional Dissection for Molecular Analysis
Published on: December 5, 2020
Spinocerebellar ataxia type 12
Elizabeth O'Hearn1, Susan E Holmes, Russell L Margolis
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. eohearn@jhmi.edu
Handbook of Clinical Neurology
|August 11, 2011
Summary
Spinocerebellar ataxia type 12 (SCA12) is a progressive neurological disorder caused by a mutation in the PPP2R2B gene. This mutation leads to abnormal Bβ expression, resulting in symptoms like action tremor and cognitive dysfunction.
Area of Science:
- Neurogenetics
- Neurology
- Molecular Biology
Background:
- Spinocerebellar ataxia type 12 (SCA12) is a late-onset, autosomal dominant neurological disorder.
- The typical presentation includes action tremor, progressing to ataxia, hyperreflexia, parkinsonism, anxiety, depression, and cognitive dysfunction.
Purpose of the Study:
- To investigate the genetic basis and clinical manifestations of Spinocerebellar Ataxia type 12 (SCA12).
- To explore the molecular mechanism underlying SCA12, focusing on the PPP2R2B gene mutation.
Main Methods:
- Genetic linkage analysis identified a CAG repeat expansion in exon 7 of the PPP2R2B gene in SCA12 patients.
- Analysis of CAG repeat lengths in normal individuals (7-28) versus SCA12 patients (55-78).
- In vitro studies investigating the promoter function of the CAG expansion and its effect on Bβ expression.
Main Results:
- SCA12 is associated with a CAG repeat expansion in the PPP2R2B gene, encoding a subunit of protein phosphatase 2A (PP2A).
- CAG repeat length correlates with increased Bβ expression, though polyglutamine production is not evident.
- Identified SCA12 kindreds in North America and Northern India, with rare reports in Singapore and China.
Conclusions:
- SCA12 is linked to a specific genetic mutation in PPP2R2B, characterized by CAG repeat expansion.
- The mutation leads to altered Bβ expression, contributing to the disorder's phenotype.
- SCA12 should be considered in patients presenting with action tremor and subsequent cerebellar and cortical dysfunction.
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