Navegando por Autor "Gonçalves, João Pedro Nunes"
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Artigo CAG repeats ≥ 34 in Ataxin-1 gene are associated with amyotrophic lateral sclerosis in a Brazilian cohort(Elsevier, 2020) Dourado Junior, Mário Emílio Teixeira; Gonçalves, João Pedro Nunes; Andrade, Helen Maia Tavares de; Cintra, Vívian Pedigone; et, al; https://orcid.org/0000-0002-9462-2294Little 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.Artigo Genetic epidemiology of familial ALS in Brazil(Elsevier, 2021) Dourado Junior, Mário Emílio Teixeira; Gonçalves, João Pedro Nunes; Leoni, Tauana Bernardes; Martins, Melina Pazian; Peluzzo, Thiago Mazzo; Saute, Jonas Alex M.; Covaleski, Anna Paula Paranhos Miranda; Oliveira, Acary Souza Bulle de; Claudino, Rinaldo; Marques Jr, Wilson; Nucci, Anamarli; França Jr, Marcondes C.; https://orcid.org/0000-0002-9462-2294Many genes associated with familial forms of the amyotrophic lateral sclerosis (fALS) have been identified in European and North American cohorts. However, little is known about the genetic bases of fALS in Latin America and Brazil, in particular. To address this question, we recruited 107 patients with fALS from 93 unrelated families from Southeastern, Southern, and Northeastern regions of the country. A 3-step diagnostic approach was used: 1) Triplet repeat primed polymerase chain reaction to search for C9orf72 expansions, then 2) fragment digestion to search for the c.166 C>T VAPB variant, and finally, 3) whole exome sequencing for those who tested negative. We identified the genetic cause for fALS in 70% of the families. VAPB and C9orf72 were the most frequent genes (30% and 22%, respectively), followed by SOD1, TARDBP, ANXA11, and FUS. Five novel variants in known ALS genes were found, including the SOD1 Val120Leu and ANXA11 Asp40Tyr, which were seen in 2 unrelated families each. In conclusion, VAPB and then C9orf72 are the genes most commonly related to fALS in Brazil.