Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant neurodegenerative disorder that is described in the pedigrees of German-American and Indian descent. The phenotype typically begins with tremor in the fourth decade, progressing to include ataxia and other cerebellar and cortical signs. SCA12 is associated with an expansion of a CAG repeat in the 5' region of the gene PPP2R2B, which encodes a brain-specific regulatory sub unit of the protein phosphatase PP2A. The repeat size ranges from 55-78 triplets in the mutant allele of affected individuals, and from 7-31 triplets in normal alleles. It is possible that an expansion mutation in PPP2R2B may influence PPP2R2B expression, perhaps altering the activity of PP2A, an enzyme implicated in multiple cellular functions, including cell cycle regulation, tau phosphorylation, and apoptosis. They cannot usually be distinguished based on clinical features alone, but 16 distinct SCAs to date have been identified with the elucidation of the genetic basis for each. Therapy for essential tremor is helpful in some cases. Psychiatric symptoms, which may cause significant morbidity in SCA12 and other SCAs, are successfully managed in SCA12 with anxiolytic and antidepressant medicines. Other palliative treatments, including social support, physical therapy, and occupational therapy help maximize patient functional capacity.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology