CAG repeats ≥ 34 in Ataxin-1 gene are associated with amyotrophic lateral sclerosis in a Brazilian cohort

• Published in: Journal of the neurological sciences 2020-07, Vol.414, p.116842-116842, Article 116842
• Main Authors: Gonçalves, João Pedro Nunes, de Andrade, Helen Maia Tavares, Cintra, Vívian Pedigone, Bonadia, Luciana Cardoso, Leoni, Tauana Bernardes, de Albuquerque, Milena, Martins, Melina Pazian, de Borba, Fabrício Castro, Couteiro, Rafael Esteves Duarte, de Oliveira, Daniel Sabino, Claudino, Rinaldo, Gonçalves, Marcos Vinicius Magno, Dourado, Mario Emilio, de Souza, Leonardo Cruz, Teixeira, Antônio Lúcio, de Godoy Rousseff Prado, Laura, Tumas, Vitor, Oliveira, Acary Souza Bulle, Nucci, Anamarli, Lopes-Cendes, Iscia, Marques, Wilson, França, Marcondes C.
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; association study; ataxin-1; Ataxin-1 - genetics; Ataxin-2 - genetics; Brazil; Europe; Genetic Association Studies; Humans; populational genetics; Trinucleotide Repeat Expansion - genetics
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2020.116842

Little is known about the genetic basis of amyotrophic lateral sclerosis (ALS) outside Europe and US. In this study, we investigated whether intermediate CAG expansions at ATXN1 were associated to ALS in the Brazilian population. To accomplish that, representative samples from 411 unrelated patients and 436 neurologically normal controls from 6 centers spread over the territory were genotyped to quantify ATXN1 expansions. We found that ATXN1 intermediate-length expansion (≥34 CAG repeats) are associated with the disease (odds ratio = 2.19, 95% CI = 1.081–4.441, p = .026). Most ATXN1-positive patients had classical phenotype, but some of them presented predominant lower motor neuron involvement. None of them had associated ataxia. Frontotemporal dementia was concomitantly found in 12.5% of patients carrying the intermediate ATXN1 expansion. Further studies are needed to validate these findings and to understand the pathophysiological mechanisms that connect ataxin-1 and ALS. •In Brazil, ATXN1 intermediate CAG repeats were found in 5.84% patients vs 2.75% controls (p = .026).•ATXN1 intermediate expansions were associated with an increased risk for ALS (OR = 2.191).•No specific phenotype was found in ALS patients carrying the ATXN1 intermediate expansion.