TY - JOUR
T1 - CAG repeats ≥ 34 in Ataxin-1 gene are associated with amyotrophic lateral sclerosis in a Brazilian cohort
AU - Gonçalves, João Pedro Nunes
AU - de Andrade, Helen Maia Tavares
AU - Cintra, Vívian Pedigone
AU - Bonadia, Luciana Cardoso
AU - Leoni, Tauana Bernardes
AU - de Albuquerque, Milena
AU - Martins, Melina Pazian
AU - de Borba, Fabrício Castro
AU - Couteiro, Rafael Esteves Duarte
AU - de Oliveira, Daniel Sabino
AU - Claudino, Rinaldo
AU - Gonçalves, Marcos Vinicius Magno
AU - Dourado, Mario Emilio
AU - de Souza, Leonardo Cruz
AU - Teixeira, Antônio Lúcio
AU - de Godoy Rousseff Prado, Laura
AU - Tumas, Vitor
AU - Oliveira, Acary Souza Bulle
AU - Nucci, Anamarli
AU - Lopes-Cendes, Iscia
AU - Marques, Wilson
AU - França, Marcondes C.
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/7/15
Y1 - 2020/7/15
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis
KW - association study
KW - ataxin-1
KW - populational genetics
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U2 - 10.1016/j.jns.2020.116842
DO - 10.1016/j.jns.2020.116842
M3 - Article
C2 - 32339968
AN - SCOPUS:85083654273
SN - 0022-510X
VL - 414
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
M1 - 116842
ER -