Glucocerebrosidase gene variants in parkinsonian patients with Machado Joseph/spinocerebellar ataxia 3

M. Siebert, K. C. Donis, M. Socal, C. R.M. Rieder, V. E. Emmel, F. Vairo, K. Michelin-Tirelli, M. França, A. C. D'Abreu, C. Bettencourt, M. Lima, I. Lopes Cendes, M. L. Saraiva-Pereira, L. B. Jardim

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3) may rarely presents a parkinsonian phenotype. Considering that mutations in the glucocerebrosidase (GBA) gene have been associated with Parkinson disease, we investigated whether these would be more prevalent in MJD/SCA3 patients with parkinsonian manifestations than in those without them. Methods: MJD/SCA3 patients with parkinsonian features were identified and compared to relatives and to a MJD/SCA3 control group with no such features. The GBA gene was sequenced and, in a subset of patients and in normal volunteers, GBA enzyme activity was measured. Results: We have identified nine index MJD/SCA3 patients with parkinsonian manifestations. Overall, GBA sequence variations were found in 3/9 MJD/SCA3 index cases with parkinsonian manifestations (33%) and in 0/40 MJD/SCA3 controls without parkinsonism (p=. 0.03, Fisher exact test). The GBA sequence variations found were p.K(-27)R, p.E326K, and p.T369M. The latter two sequence variations were also found in two symptomatic relatives with no parkinsonian manifestations. A MJD/SCA3 relative belonging to the first positive pedigree and carrier of the p.K(-27)R mutation also presented parkinsonian manifestations. GBA activity in MJD/SCA3 patients was similar to those found in the normal control group. Conclusion: Sequence variations at the GBA gene may play a role as a minor, modifying gene of MJD/SCA3 phenotype. This hypothetical role was not related to changes in GBA activity in peripheral leukocytes.

Original languageEnglish (US)
Pages (from-to)185-190
Number of pages6
JournalParkinsonism and Related Disorders
Issue number2
StatePublished - Feb 2012
Externally publishedYes


  • Gaucher disease
  • Glucocerebrosidase gene
  • Machado Joseph disease
  • Parkinson disease
  • Spinocerebellar ataxia 3

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology


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