Human Genetics

, Volume 104, Issue 6, pp 516–522

Spinocerebellar ataxias in Spanish patients: genetic analysis of familial and sporadic cases

  • Miguel Angel Pujana
  • Jordi Corral
  • Mònica Gratacòs
  • Onofre Combarros
  • José Berciano
  • David Genís
  • Isabel Banchs
  • Xavier Estivill
  • Víctor Volpini
  • The Ataxia Study Group
Original investigation

DOI: 10.1007/s004390050997

Cite this article as:
Pujana, M., Corral, J., Gratacòs, M. et al. Hum Genet (1999) 104: 516. doi:10.1007/s004390050997

Abstract

Autosomal dominant cerebellar ataxias (ADCA) are a clinically heterogeneous group of neurodegenerative disorders caused by unstable CAG repeat expansions encoding polyglutamine tracts. Five spinocerebellar ataxia genes (SCA1, SCA2, SCA3, SCA6 and SCA7) and another related dominant ataxia gene (DRPLA) have been cloned, allowing the genetic classification of these disorders. We present here the molecular analysis of 87 unrelated familial and 60 sporadic Spanish cases of spinocerebellar ataxia. For ADCA cases 15% were SCA2, 15% SCA3, 6% SCA1, 3% SCA7, 1% SCA6 and 1% DRPLA, an extremely rare mutation in Caucasoid populations. About 58% of ADCA cases remained genetically unclassified. All the SCA1 cases belong to the same geographical area and share a common haplotype for the SCA1 mutation. The expanded alleles ranged from 41 to 59 repeats for SCA1, 17 to 29 for SCA2, 67 to 77 for SCA3, and 38 to 113 for SCA7. One SCA6 case had 25 repeats and one DRPLA case had 63 repeats. The highest CAG repeat variation in meiotic transmission of expanded alleles was detected in SCA7, this being of +67 units in one paternal transmission and giving rise to a 113 CAG repeat allele in a patient who died at 3 years of age. Meiotic transmissions have also shown a tendency to more frequent paternal transmission of expanded alleles in SCA1 and maternal in SCA7. All SCA1 and SCA2 expanded alleles analyzed consisted of pure CAG repeats, whereas normal alleles were interrupted by 1–2 CAT trinucleotides in SCA1, except for three alleles of 6, 14 and 21 CAG repeats, and by 1–3 CAA trinucleotides in SCA2. No SCA or DRPLA mutations were detected in the 60 sporadic cases of spinocerebellar ataxia, but one late onset patient was identified as a recessive form due to GAA-repeat expansions in the Friedreich’s ataxia gene.

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • Miguel Angel Pujana
    • 1
  • Jordi Corral
    • 1
  • Mònica Gratacòs
    • 1
  • Onofre Combarros
    • 2
  • José Berciano
    • 2
  • David Genís
    • 3
  • Isabel Banchs
    • 1
  • Xavier Estivill
    • 1
  • Víctor Volpini
    • 1
  • The Ataxia Study Group
  1. 1.Molecular Genetics Department, Medical and Molecular Genetics Centre-IRO, Hospital Duran i Reynals, Autovía de Castelldefels km 2.7, 08907, L’Hospitalet de Llobregat, Barcelona, Spain e-mail: vvolpini@iro.es, Tel.: +34-3-2607775, Fax: +34-3-2607776ES
  2. 2.Service of Neurology, University Hospital, Marqués de Valdecilla, Santander, SpainES
  3. 3.Neurology Unit, Hospital de Girona Dr. Josep Trueta, Girona, SpainES

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