Clinical Features and Pathogenetic Mechanisms

Spinocerebellar Ataxia 12 (SCA12) is a rare disease that was first identified in a family in the United States. Patients suffered from classical spinocerebellar ataxia symptoms with an age of disease onset ranging from 8-55 years. A trinucleotide (CAG) repeat expansion was confirmed in all the affected individuals. The CAG expansion mapped to the 5’ untranslated region (UTR) of the PPP2R2B gene. This gene encodes a regulatory subunit, B of the heterotrimeric protein phosphatase 2A (PP2A). The function of this particular PP2A complex is not well understood, and the underlying molecular mechanism of SCA12 remains unclear. Additional pedigrees have been identified throughout the world but SCA12 remains a rare disease. In this chapter we will discuss the clinical manifestation of the disease and the known functions of the PP2A regulator B.