title: Glucocerebrosidase gene variants in parkinsonian patients with Machado Joseph/spinocerebellar ataxia 3.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Biotechnology Centre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: M
authors: M
authors: Siebert
authors: K C
authors: KC
authors: Donis
authors: M
authors: M
authors: Socal
authors: C R M
authors: CR
authors: Rieder
authors: V E
authors: VE
authors: Emmel
authors: F
authors: F
authors: Vairo
authors: K
authors: K
authors: Michelin-Tirelli
authors: M
authors: M
authors: França
authors: A C
authors: AC
authors: D'Abreu
authors: C
authors: C
authors: Bettencourt
authors: M
authors: M
authors: Lima
authors: I
authors: I
authors: Lopes Cendes
authors: M L
authors: ML
authors: Saraiva-Pereira
authors: L B
authors: LB
authors: Jardim
mesh_terms: D000328:Adult; D005260:Female; D014644:Genetic Variation; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D017827:Machado-Joseph Disease / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000201:enzymology* / Q000235:genetics*; D010375:Pedigree
chemical_list: D005962:Glucosylceramidase