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

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.