Expansion of a novel CAG trinucleotide repeat in the 5′ region of PPP2R2B is associated with SCA12

Abstract

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.

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Figure 1: CAG expansion in pedigree R.
Figure 2: Analysis of CAG repeat.

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Acknowledgements

We thank family members and their physicians for cooperation; T. Swift-Scanlan, S. Wang, L. Monfredo, V. Willour, F. Guarnieri, B. Hemmings, B. Wadzinski, O.C. Stine, S. Reich and A. Scott for assistance; R. Seeger for LA-N-1 cells for control experiments; L. Schoels, S. Krueger and W. Berger for collection of German control subjects; and P.R. McHugh for support and encouragement. This work was supported by grants from the Huntington's Disease Society of America and NIH NS16375, MH01275 and MH50763.

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Correspondence to Russell L Margolis.

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Holmes, S., O'Hearn, E., McInnis, M. et al. Expansion of a novel CAG trinucleotide repeat in the 5′ region of PPP2R2B is associated with SCA12. Nat Genet 23, 391–392 (1999). https://doi.org/10.1038/70493

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