Neurogenetics

, Volume 1, Issue 1, pp 59–64

SCA2 trinucleotide expansion in German SCA patients

  • Olaf Riess
  • Franco A. Laccone
  • Suzana Gispert
  • Ludger Schöls
  • Christine Zühlke
  • Ana Maria Menezes Vieira-Saecker
  • Susanne Herlt
  • Karl Wessel
  • Jörg T. Epplen
  • Bernhard H.F. Weber
  • Friedmar Kreuz
  • Soheyla Chahrokh-Zadeh
  • Alfons Meindl
  • Astrid Lunkes
  • Jorge Aguiar
  • Milan Macek Jr
  • Alice Krebsová
  • Milan Macek Sen
  • Katrin Bürk
  • Sigrid Tinschert
  • Isolde Schreyer
  • Stefan-M. Pulst
  • Georg Auburger
ORIGINAL ARTICLE

DOI: 10.1007/s100480050009

Cite this article as:
Riess, O., Laccone, F., Gispert, S. et al. Neurogenetics (1997) 1: 59. doi:10.1007/s100480050009

ABSTRACT

Autosomal dominant spinocerebellar ataxias (SCA) are a group of clinically and genetically heterogeneous neurodegenerative disorders which lead to progressive cerebellar ataxia. A gene responsible for SCA type 2 has been mapped to human chromosome 12 and the disease causing mutation has been identified as an unstable and expanded (CAG)n trinucleotide repeat. We investigated the (CAG)n repeat length of the SCA2 gene in 842 patients with sporadic ataxia and in 96 German families with dominantly inherited SCA which do not harbor the SCA1 or MJD1/SCA3 mutation, respectively. The SCA2 (CAG)n expansion was identified in 71 patients from 54 families. The (CAG)n stretch of the affected allele varied between 36 and 64 trinucleotide units. Significant repeat expansions occurred most commonly during paternal transmission. Analysis of the (CAG)n repeat lengths with the age of onset in 41 patients revealed an inverse correlation. Two hundred and forty-one apparently healthy octogenerians carried alleles between 16 and 31 repeats. One 50-year old, healthy individual had 34 repeats; she had transmitted an expanded allele to her child. The small difference between ‘normal’ and disease alleles makes it necessary to define the extreme values of their ranges. With one exception, the trinucleotide expansion was not observed in 842 ataxia patients without a family history of the disease. The SCA2 mutation causes the disease in nearly 14% of autosomal dominant SCA in Germany.

Keywords: spinocerebellar ataxia, SCA2, trinucleotide repeat expansion, octogenarians, repeat instability 

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • Olaf Riess
    • 1
  • Franco A. Laccone
    • 2
  • Suzana Gispert
    • 3
  • Ludger Schöls
    • 4
  • Christine Zühlke
    • 5
  • Ana Maria Menezes Vieira-Saecker
    • 1
  • Susanne Herlt
    • 2
  • Karl Wessel
    • 6
  • Jörg T. Epplen
    • 1
  • Bernhard H.F. Weber
    • 7
  • Friedmar Kreuz
    • 8
  • Soheyla Chahrokh-Zadeh
    • 9
  • Alfons Meindl
    • 9
  • Astrid Lunkes
    • 3
  • Jorge Aguiar
    • 3
  • Milan Macek Jr
    • 10
  • Alice Krebsová
    • 10
  • Milan Macek Sen
    • 10
  • Katrin Bürk
    • 11
  • Sigrid Tinschert
    • 12
  • Isolde Schreyer
    • 13
  • Stefan-M. Pulst
    • 14
  • Georg Auburger
    • 3
  1. 1.Molecular Human Genetics, Ruhr-University, D-44780 Bochum, GermanyDE
  2. 2.Institute for Human Genetics, University Göttingen, Göttingen, GermanyDE
  3. 3.Division of Neurology, University Hospital, D-40225 Düsseldorf, GermanyDE
  4. 4.Department of Neurology, St. Josef Hospital, Bochum, GermanyDE
  5. 5.Institute for Human Genetics, University Lübeck, Lübeck, GermanyDE
  6. 6.Clinic of Neurology, University Lübeck, Lübeck, GermanyDE
  7. 7.Institute for Human Genetics, Biocenter, University Würzburg, Würzburg, GermanyDE
  8. 8.Institute of Clinical Genetics, University Hospital, Technical University, Dresden, GermanyDE
  9. 9.Division of Pediatric Genetics, Childrens Hospital, Ludwig-Maximilians-University, Munich, GermanyDE
  10. 10.Department of Medical Genetics II, University Hospital Praha, Czech RepublicCS
  11. 11.Department of Neurology, University Tübingen, Tübingen, GermanyDE
  12. 12.Institute for Human Genetics, Charité Hospital, Humboldt-University, Berlin, GermanyDE
  13. 13.Institute for Human Genetics, University Jena, Jena, GermanyDE
  14. 14.The Rose Moss Laboratory for Parkinson's and Neurodegenerative Diseases, Division of Neurology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, USAUS

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