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

Raphael Machado de Castilhos, Gabriel Vasata Furtado, Tailise Conte Gheno, Paola Schaeffer, Aline Russo, Orlando Barsottini, José Luiz Pedroso, Diego Z. Salarini, Fernando Regla Vargas, Maria Angélica de Faria Domingues de Lima, Clécio Godeiro, Luiz Carlos Santana-da-Silva, Maria Betânia Pereira Toralles, Silvana Santos, Hélio van der Linden, Hector Yuri Wanderley, Paula Frassineti Vanconcelos de Medeiros, Eliana Ternes Pereira, Erlane Ribeiro, Maria Luiza Saraiva-Pereira, Laura Bannach Jardim, on behalf of Rede Neurogenetica

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.