Spinocerebellar Ataxias in Brazil-Frequencies and Modulating Effects of Related Genes

This study describes the frequency of spinocerebellar ataxias and of CAG repeats range in different geographical regions of Brazil, and explores the hypothetical role of normal CAG repeats at ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7 genes on age at onset and on neurological findings. Patients with symptoms and family history compatible with a SCA were recruited in 11 cities of the country; clinical data and DNA samples were collected. Capillary electrophoresis was performed to detect CAG lengths at SCA1, SCA2, SCA3/MJD, SCA6, SCA7, SCA12, SCA17, and DRPLA associated genes, and a repeat primed PCR was used to detect ATTCT expansions at SCA10 gene. Five hundred forty-four patients (359 families) were included. There were 214 SCA3/MJD families (59.6 %), 28 SCA2 (7.8 %), 20 SCA7 (5.6 %), 15 SCA1 (4.2 %), 12 SCA10 (3.3 %), 5 SCA6 (1.4 %), and 65 families without a molecular diagnosis (18.1 %). Divergent rates of SCA3/MJD, SCA2, and SCA7 were seen in regions with different ethnic backgrounds. 64.7 % of our SCA10 patients presented seizures. Among SCA2 patients, longer ATXN3 CAG alleles were associated with earlier ages at onset (p<0.036, linear regression). A portrait of SCAs in Brazil was obtained, where variation in frequencies seemed to parallel ethnic differences. New potential interactions between some SCA-related genes were presented.FAPERGSConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)INAGEMPFIPE-HCPAHosp Clin Porto Alegre, Med Genet Serv, BR-90035903 Porto Alegre, RS, BrazilHosp Clin Porto Alegre, Lab Genet Identificat, BR-90035903 Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, UNIFESP Escola Paulista Med, Disciplina Neurol Clin, Setor Neurol Geral & Ataxias, São Paulo, BrazilDisciplina Neurol Santa Casa São Paulo, São Paulo, BrazilUniv Fed Estado Rio de Janeiro, Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Postgrad Program, Rio de Janeiro, BrazilInst Nacl Canc, Genet Counseling Program, Rio de Janeiro, BrazilUniv Fed Rio Grande do Norte, BR-59072970 Natal, RN, BrazilFed Univ Para, Inst Ciencias Biol, Lab Erros Inatos Metab, BR-66059 Belem, Para, BrazilUniv Fed Bahia, Salvador, BA, BrazilUniv Estadual Paraiba, Campina Grande, BrazilCtr Reabilitacao Dr Henrique Santillo, Goiania, Go, BrazilAPAE Vitoria, Espirito Santo, BrazilUniv Fed Campina Grande, Paraiba, BrazilUniv Fed Santa Catarina, Florianopolis, SC, BrazilAssoc Cearense Doencas Genet, Fortaleza, Ceara, BrazilUniv Fed Rio Grande do Sul, Dept Internal Med, Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Postgrad Program Med Sci, Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Postgrad Program Genet & Mol Biol, Porto Alegre, RS, BrazilInst Nacl Genet Med Populac INAGEMP, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, UNIFESP Escola Paulista Med, Disciplina Neurol Clin, Setor Neurol Geral & Ataxias, São Paulo, BrazilWeb of Scienc