TY - JOUR
T1 - Intrafamilial variability of Parkinson phenotype in SCAs
T2 - Novel cases due to SCA2 and SCA3 expansions
AU - Socal, M. P.
AU - Emmel, V. E.
AU - Rieder, C. R.M.
AU - Hilbig, A.
AU - Saraiva-Pereira, M. L.
AU - Jardim, L. B.
N1 - Funding Information:
We are grateful to the patients and their relatives who agreed to participate in this project. This study was supported by CNPq, FAPERGS, and FIPE-HCPA. V. Emmel and Profs. L.B. Jardim and M.L. Saraiva-Pereira were supported by CNPq.
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/6
Y1 - 2009/6
N2 - Background: Parkinson's disease (PD) has been related to mutations associated with spinocerebellar ataxias (SCA); the frequency of the diagnosis of these mutations is low in general late-onset PD cases. Our aim was to investigate a selected high-risk group of PD patients. Methods: PD patients with autosomal dominant inheritance or atypical neurological manifestations were enrolled, underwent a full neurological examination and had the CAG tracts of their SCA1, 2, 3, 6 and 7 genes analyzed. Results: Of the 23 studied families, two SCA3 and one SCA2 cases were identified. All had autosomal dominant inheritance. In the SCA2 pedigree, four affected sibs had a homogeneous PD phenotype. CAG repeats varied between 35 and 44 with CAA interruptions. Intrafamilial phenotypic heterogeneity was identified in the SCA3 pedigrees; parkinsonian and ataxic phenotypes coexisted in both kindreds. CAGn varied between 69 and 71 repeats. Age of onset was lower in the SCA3 patients than in the remaining 24 cases (38 versus 46.7 ± 12 years of age, p = 0.003). Conclusions: SCA2 and SCA3 mutations were detected in 13% of the present sample: the strategy of selecting a high-risk group increased the rate of making these diagnoses. The SCA2 cases confirmed an association between PD and interrupted expansions, as well as PD intrafamilial phenotypic homogeneity. Clinical heterogeneity of SCA3 pedigrees suggests that disease-modifying agents outside the MJD1 gene may play a role in determining PD symptoms in this disorder.
AB - Background: Parkinson's disease (PD) has been related to mutations associated with spinocerebellar ataxias (SCA); the frequency of the diagnosis of these mutations is low in general late-onset PD cases. Our aim was to investigate a selected high-risk group of PD patients. Methods: PD patients with autosomal dominant inheritance or atypical neurological manifestations were enrolled, underwent a full neurological examination and had the CAG tracts of their SCA1, 2, 3, 6 and 7 genes analyzed. Results: Of the 23 studied families, two SCA3 and one SCA2 cases were identified. All had autosomal dominant inheritance. In the SCA2 pedigree, four affected sibs had a homogeneous PD phenotype. CAG repeats varied between 35 and 44 with CAA interruptions. Intrafamilial phenotypic heterogeneity was identified in the SCA3 pedigrees; parkinsonian and ataxic phenotypes coexisted in both kindreds. CAGn varied between 69 and 71 repeats. Age of onset was lower in the SCA3 patients than in the remaining 24 cases (38 versus 46.7 ± 12 years of age, p = 0.003). Conclusions: SCA2 and SCA3 mutations were detected in 13% of the present sample: the strategy of selecting a high-risk group increased the rate of making these diagnoses. The SCA2 cases confirmed an association between PD and interrupted expansions, as well as PD intrafamilial phenotypic homogeneity. Clinical heterogeneity of SCA3 pedigrees suggests that disease-modifying agents outside the MJD1 gene may play a role in determining PD symptoms in this disorder.
KW - Dominant inheritance
KW - Parkinson's disease
KW - SCA2
KW - SCA3
KW - Spinocerebellar ataxia
UR - http://www.scopus.com/inward/record.url?scp=67349277693&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349277693&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2008.09.005
DO - 10.1016/j.parkreldis.2008.09.005
M3 - Article
C2 - 18990604
AN - SCOPUS:67349277693
SN - 1353-8020
VL - 15
SP - 374
EP - 378
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 5
ER -