Neurological phenotypes in spinocerebellar ataxia type 2: Role of mitochondrial polymorphism A10398G and other risk factors

Neurological phenotypes in spinocerebellar ataxia type 2: Role of mitochondrial polymorphism A10398G and other risk factors

Author Monte, Thais Lampert Google Scholar
Pereira, Fernanda Santos Google Scholar
Reckziegel, Estela da Rosa Google Scholar
Augustin, Marina Coutinho Google Scholar
Locks-Coelho, Lucas Doridio Google Scholar
Santos, Amanda Senna P. Google Scholar
Pedroso, Jose Luiz Autor UNIFESP Google Scholar
Barsottini, Orlando Autor UNIFESP Google Scholar
Vargas, Fernando Regla Google Scholar
Saraiva-Pereira, Maria-Luiza Google Scholar
Jardim, Laura Bannach Google Scholar
Abstract Background: Spinocerebellar ataxia type 2 (SCA2) is due to a CAG expansion (CAGexp) at ATXN2. SCA2 presents great clinical variability, alongside characteristic ataxia with saccadic slowness. Aims: To study parkinsonism, dementia, dystonia, and amyotrophy as subphenotypes of SCA2, and to explore the effect of CAG repeats at different loci and of mitochondrial polymorphism A10398G as modifiers of phenotype. Methods: Symptomatic subjects were classified by presence/absence of neurological signs mentioned above

SARA and NESSCA scores were obtained. CAG repeats at A1XN1, ATXN2, ATXN3, CACNA1A, ATXN7 and RAI1, and polymorphism A10398G at mtDNA were established. Group characteristics were compared, with a p< 0.05. Results: Forty-eight SCA2 individuals were included. Age at onset, CAGexp, and disease duration explained 53% and 43% of SARA and NESSCA variations, respectively. CAGexp of subjects with and without parkinsonism were different (medians of 42 and 39 repeats) as well as of subjects with and without dystonia (44 and 40 repeats). Amyotrophy was not significantly related to any variable under study. Concerning polymorphism A10398G, 83% of subjects with and 34% of those without cognitive decline carried 10398G at (p = 0.003). Discussion: Treating the four phenotypic subgroups as outcomes was a valid strategy to identify modifiers of disease. Among correlations found, some confirmed previous reports, such as that between dystonia and CAGexp. Of note was the association between cognitive decline and the variant G at mitochondrial polymorphism A10398G, a variant formerly related to earlier ages at onset in SCA2. (c) 2017 Elsevier Ltd. All rights reserved.
Keywords Amyotrophy
A10398G polymorphism
Cognitive decline
Spinocerebellar ataxia type 2
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundo de Incentivo a Pesquisa do Hospital de Clinicas de Porto Alegre (FIPE-HCPA)
Instituto Nacional de Genetica Medica Populacional (INAGEMP)
Grant number CNPq: 78057/2012-1
HCPA: 12-0357
HCPA: 12-0396
Date 2017
Published in Parkinsonism & Related Disorders. Oxford, v. 42, p. 54-60, 2017.
ISSN 1353-8020 (Sherpa/Romeo, impact factor)
Publisher Elsevier Sci Ltd
Extent 54-60
Access rights Closed access
Type Article
Web of Science ID WOS:000415392900008

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