Expansion of a Novel CAG Trinucleotide Repeat in the 5′ Region of PPP2R2B is Associated with SCA12

The genetic aetiologies of at least 20% of autosomal dominant spinocerebellar ataxias (SCAs) have yet to be elucidated1. We have recently identified a novel form of autosomal dominant SCA, termed SCA12, in a large pedigree ('R') of German descent. The phenotype is variable, but the prototypical phenotype is that of a classic spinocerebellar ataxia, and the disease resembles the spinocerebellar ataxias more closely than any other form of neurodegenerative disorder. Age of onset ranges from 8 to 55 years. Most individuals present in the fourth decade with upper extremity tremor, progressing over several decades to include head tremor, gait ataxia, dysmetria, dysdiadokinesis, hyperreflexia, paucity of movement, abnormal eye movements and, in the oldest subjects, dementia. MRI or CT scans of five cases indicate both cortical and cerebellar atrophy.