Genetic epidemiology of familial ALS in Brazil.

Autor: Nunes Gonçalves JP; Departments of Neurology and Medical Genetics, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BRAZIL., Leoni TB; Departments of Neurology and Medical Genetics, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BRAZIL., Martins MP; Departments of Neurology and Medical Genetics, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BRAZIL., Peluzzo TM; Departments of Neurology and Medical Genetics, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BRAZIL., Dourado MET Jr; Department of Integrative Medicine, Federal University of Rio Grande do Norte, Natal, Brazil., Saute JAM; Department of Internal Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Brazil., Paranhos Miranda Covaleski AP; Department of Neurology, Federal University of Pernambuco, Recife, Brazil., Bulle de Oliveira AS; Department of Neurology, Neuromuscular Disorders Unit, Federal University of São Paulo, São Paulo, Brazil., Claudino R; Department of Neurology, Federal University of Santa Catarina, Florianópolis, Brazil., Marques W Jr; Department of Neurosciences and Behavior Sciences, Ribeirão Preto School of Medicine, University of São Paulo (HCFMRP-USP), Ribeirão Preto, Brazil., Nucci A; Departments of Neurology and Medical Genetics, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BRAZIL., França MC Jr; Departments of Neurology and Medical Genetics, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, BRAZIL. Electronic address: mcfjr@unicamp.br.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2021 Jun; Vol. 102, pp. 227.e1-227.e4. Date of Electronic Publication: 2021 Jan 22.
DOI: 10.1016/j.neurobiolaging.2021.01.007
Abstrakt: Many 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.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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