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Extreme Expansion Detection in Spinocerebellar Ataxia Type 2 and Type 7

  • Karen Snow
  • Rong Mao
Part of the Methods in Molecular Biology™ book series (MIMB, volume 217)

Abstract

The autosomal dominant cerebellar ataxias are each defined by progressive ataxia and variable association with other clinical findings (1). Numerous spinocerebellar ataxia (SCA) loci have been identified and several of the SCA genes have expansion of a CAG-repeat as the underlying mutation (2,3). Assays that determine the CAG-repeat length in SCA1, SCA2, SCA3, SCA6, and SCA7 are used for both diagnostic and predictive testing purposes. Molecular genetic testing is necessary to establish a diagnosis of the SCAs that do not have unique clinical features. It is also a valuable tool in confirming a clinical diagnosis of SCAs that have characteristic clinical findings (such as retinal dystrophy in SCA7) (2,3). Assays typically utilize polymerase chain reaction (PCR) amplification of the repeat region, separation of PCR products by gel electrophoresis or capillary electrophoresis, and visualization of products by incorporation of radioactivity or dye into PCR products or staining with dye after product separation (4, 5, 6).

Keywords

Polymerase Chain Reaction Product Autosomal Dominant Cerebellar Ataxia Polymerase Chain Reaction Tube Cerenkov Counting Extreme Expansion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Harding, A. E. (1982) Clinical features and classification of the late onset autosomal dominant cerebellar ataxias. Brain 105, 1–28.PubMedCrossRefGoogle Scholar
  2. 2.
    Evidente, V. G., Gwinn-Hardy, K. A., Caviness, J. N., and Gilman, S. (2000) Hereditary ataxias. Mayo Clin. Proc. 75, 475–490.PubMedCrossRefGoogle Scholar
  3. 3.
    Bird, T. D. Hereditary Ataxia Overview, in GeneClinics: Medical Genetics Knowledge Base. University of Washington, Seattle, WA, USA. Available online at http://www. geneclinics.org/profiles/ataxias. Accessed 4 February 2002. (Updated 14 June 2000)
  4. 4.
    Moseley, M.L., Benzow, K.A., Schut, L.J., Bird, T.D., Gomez, C.M., Barkhaus, P.E., et al. (1998) Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families. Neurology 51, 1666–1671.PubMedGoogle Scholar
  5. 5.
    Vuillaume, I., Schraen, S., Rousseaux, J., and Sablonniere, B. (1998) Simple nonisotopic assays for detection of (CAG)n repeats expansions associated with seven neurodegenerative disorders. Diagn. Mol. Pathol. 7, 174–179.PubMedCrossRefGoogle Scholar
  6. 6.
    Potter, N.T. and Nance, M.A. (2000) Genetic testing for ataxia in North America. Mol. Diagn. 5, 91–99.PubMedGoogle Scholar
  7. 7.
    Babovic-Vuksanovic, D., Snow, K., Patterson, M. C., and Michels, V. V. (1998) Spinocer-ebellar ataxia type 2 (SCA 2) in an infant with extreme CAG repeat expansion. Am. J. Med. Genet. 79, 383–387.PubMedCrossRefGoogle Scholar
  8. 8.
    Benton, C., de Silva, R., Rutledge, S., Bohlega, S., Ashizawa, T., and Zoghbi, H. (1998) Molecular and clinical studies in SCA-7 define a broad clinical spectrum and the infantile phenotype. Neurology 51, 1081–1086.PubMedGoogle Scholar
  9. 9.
    David, G., Durr, A., Stevanin, G., Cancel, G., Abbas, N., Benomar, A., et al. (1998) Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7). Hum. Mol. Genet. 7, 165–170.PubMedCrossRefGoogle Scholar
  10. 10.
    Johansson, J., Forsgren, L., Sandgren, O., Brice, A., Holmgren, G., and Holmberg, M. (1998) Expanded CAG repeats in Swedish spinocerebellar ataxia type 7 (SCA7) patients: effect of CAG repeat length on the clinical manifestation. Hum. Mol. Genet. 7, 171–176.PubMedCrossRefGoogle Scholar
  11. 11.
    Giunti, P., Stevanin, G., Worth, P., David, G., Brice, A., and Wood, N. (1999) Molecular and clinical study of 18 families with ADC A type II: evidence for genetic heterogeneity and de novo mutation. Am. J. Hum. Genet. 64, 1594–1603.PubMedCrossRefGoogle Scholar
  12. 12.
    Grattan-Smith, P. J., Healey, S., Grigg, J. R., and Christodoulou, J. (2001) Spinocerebellar ataxia type 7: a distinctive form of autosomal dominant cerebellar ataxia with retinopathy and marked genetic anticipation. J. Paediatr. Child. Health 37, 81–84.PubMedCrossRefGoogle Scholar
  13. 13.
    Mao, R., Aylsworth, A. S., Potter, N., Wilson, W.G., Breningstall, G., Wick, M. J., et al. Childhood-onset ataxia: testing for large CAG-repeats in SCA2 and SCA7. Am. J. Med. Genet. 110, 338–345.Google Scholar
  14. 14.
    Monckton, D. G., Cayuela, M. L., Gould, F. K., Brock, G. J., Silva, R., and Ashizawa, T. (1999) Very large (CAG)(n) DNA repeat expansions in the sperm of two spinocerebellar ataxia type 7 males. Hum. Mol. Genet. 8, 2473–2478.PubMedCrossRefGoogle Scholar
  15. 15.
    The American College of Medical Genetics/American Society of Human Genetics Hun-tington Disease Genetic Testing Working Group. (1998) ACMG/ASHG statement. Laboratory guidelines for Huntington disease genetic testing. Am. J. Hum. Genet. 62, 1243–1247.CrossRefGoogle Scholar
  16. 16.
    Guida, M., Fenwick, R. G., Papp, A. C., Snyder, P. J., Sedra, M., and Prior, T. W. (1996) Southern transfer protocol for confirmation of Huntington disease. Clin. Chem. 42, 1711–1712.PubMedGoogle Scholar
  17. 17.
    Nance, M., Mathias-Hagen, V., Breningstall, G., Wick, M., and McGlennen, R. (1999) Analysis of a very large trinucleotide repeat in a patient with juvenile Huntington’s disease. Neurology 52, 392–394.PubMedGoogle Scholar
  18. 18.
    Pulst, S-M. Spinocerebellar Ataxia Type 2, in GeneClinics: Medical Genetics Knowledge Base. University of Washington, Seattle, WA, USA. Available online at http://www. geneclinics.org/profiles/sca2. Accessed 4 February 2002. (Updated 9 January 2001)
  19. 19.
    Gouw, L. G. and Ptacek, L. J. Spinocerebellar Ataxia Type 7, in GeneClinics: Medical Genetics Knowledge Base. University of Washington, Seattle, WA, USA. Available online at http://www.geneclinics.org/profiles/sca7. Accessed 4 February 2002. (Updated 22 May 2001)
  20. 20.
    Sambrook, J., Fritsch, E. F., and Maniatis, T., eds. (1989) Molecular Cloning. A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Springs Harbor, NY, USA.Google Scholar
  21. 21.
    Moore, D. D., Preparation and analysis of DNA, in: Current Protocols in Molecular Biology (Ausubel I. and Frederick M., eds.), Unit 2.9, John Wiley & Sons, Inc., New York, NY, USA.Google Scholar
  22. 22.
    Pulst, S., Nechiporuk, A., Nechiporuk, T., Gispert, S., Chen, X., Lopes-Cendes, I., et al. (1996) Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nat. Genet. 14, 269–276.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  • Karen Snow
    • 1
  • Rong Mao
    • 2
  1. 1.Molecular Genetics Laboratory, Mayo ClinicRochester
  2. 2.DNA Diagnostic LaboratoryUniversity of Utah School of MedicineSalt Lake City

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