Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

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

Similar content being viewed by others

References

  1. Schols, L. et al. Ann. Neurol. 42, 924– 932 (1997).

    Article  CAS  Google Scholar 

  2. Schalling, M., Hudson, T.J., Buetow, K.W. & Housman, D.E. Nature Genet. 4, 135–139 (1993).

    Article  CAS  Google Scholar 

  3. Margolis, R.L., McInnis, M.G., Rosenblatt, A. & Ross, C.A. Arch. Gen. Psychiatry 56, 1019–1031 (1999).

    Article  CAS  Google Scholar 

  4. Koob, M.D. et al. Nature Genet. 18, 72– 75 (1998).

    Article  CAS  Google Scholar 

  5. Ott, J. Analysis of Human Genetic Linkage (Johns Hopkins University Press, Baltimore, 1991).

    Google Scholar 

  6. Mayer, R.E. et al. Biochemistry 30, 3589– 3597 (1991).

    Article  CAS  Google Scholar 

  7. Strack, S., Zaucha, J.A., Ebner, F.F., Colbran, R.J. & Wadzinski, B.E. J. Comp. Neurol. 392, 515–527 (1998).

    Article  CAS  Google Scholar 

  8. Millward, T.A., Zolnierowicz, S. & Hemmings, B.A. Trends Biochem. Sci. 24, 186 –191 (1999).

    Article  CAS  Google Scholar 

  9. Ince, T.A. & Scotto, K.W. J. Biol. Chem. 270, 30249–30252 (1995).

    Article  CAS  Google Scholar 

  10. Burke, T.W., Willy, P.J., Kutach, A.K., Butler, J.E. & Kadonaga, J.T. Cold Spring Harb. Symp. Quant. Biol. 63, 75–82 ( 1998).

    Article  CAS  Google Scholar 

  11. Trottier, Y. et al. Nature 378, 403–406 (1995).

    Article  CAS  Google Scholar 

  12. Mayer-Jaekel, R.E. et al. Cell 72, 621–633 (1993).

    Article  CAS  Google Scholar 

  13. Sontag, E. et al. J. Biol. Chem. 274, 25490– 25498 (1999).

    Article  CAS  Google Scholar 

  14. Deng, X., Ito, T., Carr, B., Mumby, M. & May, W.S. Jr J. Biol. Chem. 273, 34157–34163 (1998).

    Article  CAS  Google Scholar 

  15. Santoro, M.F. et al. J. Biol. Chem. 273, 13119– 13128 (1998).

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Russell L Margolis.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/70493

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing