SCA12: An unusual mutation leads to an unusual spinocerebellar ataxia

Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant neurodegene rative disorder which has been described in pedigrees of German American an d Indian descent. The phenotype typically begins with tremor in the fourth decade, progressing to include ataxia and other cerebellar and cortical sig ns. SCA12 is associated with an expansion of a CAG repeat in the 5' region of the gene PPP2R2B, which encodes a brain-specific regulatory subunit of t he protein phosphatase PP2A. The repeat size ranges from 55 to 78 triplets in the mutant allele of affected individuals, and from 9 to 28 triplets in normal alleles. It is possible that an expansion mutation in PPP2R2B may in fluence PPP2R2B expression, perhaps altering the activity of PP2A, an enzym e implicated in multiple cellular functions, including cell cycle regulatio n, tau phosphorylation, and apoptosis. (C) 2001 Elsevier Science Inc.