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
Department of Medical Genetics, School of Medicine, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", 13083-887 Campinas, SP, Brazil.
Department of Neurology, School of Medicine, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126, Cidade Universitária "Zeferino Vaz", 13083-887 Campinas, SP, Brazil.
J Neurol Sci. 2020 Jul 15;414:116842. doi: 10.1016/j.jns.2020.116842. Epub 2020 Apr 19.
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.
在欧洲和美国以外地区，人们对肌萎缩侧索硬化症（ALS）的遗传基础知之甚少。在本研究中，我们调查了ATXN1基因中等长度的CAG重复序列扩增是否与巴西人群的ALS相关。为了实现这一目标，我们对来自该国6个中心的411名无亲缘关系的患者和436名神经学正常对照的代表性样本进行了基因分型，以量化ATXN1基因的扩增情况。我们发现，ATXN1基因中等长度的扩增（≥34个CAG重复序列）与该疾病相关（优势比=2.19，95%置信区间=1.081-4.441，p=0.026）。大多数携带ATXN1基因扩增的患者具有典型的表型，但其中一些患者主要表现为下运动神经元受累。他们均无共济失调相关症状。在携带ATXN1基因中等长度扩增的患者中，12.5%同时患有额颞叶痴呆。需要进一步的研究来验证这些发现，并了解连接ataxin-1和ALS的病理生理机制。
