TY - JOUR
T1 - Glucocerebrosidase gene variants in parkinsonian patients with Machado Joseph/spinocerebellar ataxia 3
AU - Siebert, M.
AU - Donis, K. C.
AU - Socal, M.
AU - Rieder, C. R.M.
AU - Emmel, V. E.
AU - Vairo, F.
AU - Michelin-Tirelli, K.
AU - França, M.
AU - D'Abreu, A. C.
AU - Bettencourt, C.
AU - Lima, M.
AU - Lopes Cendes, I.
AU - Saraiva-Pereira, M. L.
AU - Jardim, L. B.
N1 - Funding Information:
We are grateful to patients who agreed to participate in this study. This study was supported by CNPq, CAPES, FAPERGS, FAPESP, INAGEMP, and FIPE-HCPA. França Jr M is supported by a Post-doctoral fellowship from FAPESP. Bettencourt C is supported by a Post-doctoral fellowship from FCT [SFRH/BPD/63121/2009]. Siebert M, Rieder CRM, Lopes-Cendes I, Saraiva-Pereira ML, and Jardim LB were supported by CNPq.
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - Gaucher disease
KW - Glucocerebrosidase gene
KW - Machado Joseph disease
KW - Parkinson disease
KW - Spinocerebellar ataxia 3
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U2 - 10.1016/j.parkreldis.2011.09.024
DO - 10.1016/j.parkreldis.2011.09.024
M3 - Article
C2 - 22001711
AN - SCOPUS:84856234407
SN - 1353-8020
VL - 18
SP - 185
EP - 190
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 2
ER -