Genetic epidemiology of familial ALS in Brazil
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRN |
Texto Completo: | https://repositorio.ufrn.br/handle/123456789/54159 https://doi.org/10.1016/j.neurobiolaging.2021.01.007 |
Resumo: | 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. |
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Dourado Junior, Mário Emílio TeixeiraGonçalves, João Pedro NunesLeoni, Tauana BernardesMartins, Melina PazianPeluzzo, Thiago MazzoSaute, Jonas Alex M.Covaleski, Anna Paula Paranhos MirandaOliveira, Acary Souza Bulle deClaudino, RinaldoMarques Jr, WilsonNucci, AnamarliFrança Jr, Marcondes C.https://orcid.org/0000-0002-9462-22942023-07-25T18:41:03Z2023-07-25T18:41:03Z2021GONÇALVES, João Pedro Nunes; LEONI, Tauana Bernardes; MARTINS, Melina Pazian; PELUZZO, Thiago Mazzo; DOURADO, Mario Emílio T.; SAUTE, Jonas Alex M.; COVALESKI, Anna Paula Paranhos Miranda; OLIVEIRA, Acary Souza Bulle de; CLAUDINO, Rinaldo; MARQUES, Wilson. Genetic epidemiology of familial ALS in Brazil. Neurobiology Of Aging, [S.L.], v. 102, p. 227-227, jun. 2021. Elsevier BV. http://dx.doi.org/10.1016/j.neurobiolaging.2021.01.007. Disponível em: https://www.sciencedirect.com/science/article/pii/S0197458021000142?via%3Dihub. Acesso em: 13 jul. 2023.https://repositorio.ufrn.br/handle/123456789/54159https://doi.org/10.1016/j.neurobiolaging.2021.01.007Elsevieramyotrophic lateral sclerosisgeneticswhole exome sequencingVAPBGenetic epidemiology of familial ALS in Brazilinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleMany 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.engreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81484https://repositorio.ufrn.br/bitstream/123456789/54159/2/license.txte9597aa2854d128fd968be5edc8a28d9MD52123456789/541592023-07-25 15:41:19.084oai:https://repositorio.ufrn.br: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Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2023-07-25T18:41:19Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false |
dc.title.pt_BR.fl_str_mv |
Genetic epidemiology of familial ALS in Brazil |
title |
Genetic epidemiology of familial ALS in Brazil |
spellingShingle |
Genetic epidemiology of familial ALS in Brazil Dourado Junior, Mário Emílio Teixeira amyotrophic lateral sclerosis genetics whole exome sequencing VAPB |
title_short |
Genetic epidemiology of familial ALS in Brazil |
title_full |
Genetic epidemiology of familial ALS in Brazil |
title_fullStr |
Genetic epidemiology of familial ALS in Brazil |
title_full_unstemmed |
Genetic epidemiology of familial ALS in Brazil |
title_sort |
Genetic epidemiology of familial ALS in Brazil |
author |
Dourado Junior, Mário Emílio Teixeira |
author_facet |
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. |
author_role |
author |
author2 |
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. |
author2_role |
author author author author author author author author author author author |
dc.contributor.authorID.pt_BR.fl_str_mv |
https://orcid.org/0000-0002-9462-2294 |
dc.contributor.author.fl_str_mv |
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. |
dc.subject.por.fl_str_mv |
amyotrophic lateral sclerosis genetics whole exome sequencing VAPB |
topic |
amyotrophic lateral sclerosis genetics whole exome sequencing VAPB |
description |
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. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021 |
dc.date.accessioned.fl_str_mv |
2023-07-25T18:41:03Z |
dc.date.available.fl_str_mv |
2023-07-25T18:41:03Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
GONÇALVES, João Pedro Nunes; LEONI, Tauana Bernardes; MARTINS, Melina Pazian; PELUZZO, Thiago Mazzo; DOURADO, Mario Emílio T.; SAUTE, Jonas Alex M.; COVALESKI, Anna Paula Paranhos Miranda; OLIVEIRA, Acary Souza Bulle de; CLAUDINO, Rinaldo; MARQUES, Wilson. Genetic epidemiology of familial ALS in Brazil. Neurobiology Of Aging, [S.L.], v. 102, p. 227-227, jun. 2021. Elsevier BV. http://dx.doi.org/10.1016/j.neurobiolaging.2021.01.007. Disponível em: https://www.sciencedirect.com/science/article/pii/S0197458021000142?via%3Dihub. Acesso em: 13 jul. 2023. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufrn.br/handle/123456789/54159 |
dc.identifier.doi.none.fl_str_mv |
https://doi.org/10.1016/j.neurobiolaging.2021.01.007 |
identifier_str_mv |
GONÇALVES, João Pedro Nunes; LEONI, Tauana Bernardes; MARTINS, Melina Pazian; PELUZZO, Thiago Mazzo; DOURADO, Mario Emílio T.; SAUTE, Jonas Alex M.; COVALESKI, Anna Paula Paranhos Miranda; OLIVEIRA, Acary Souza Bulle de; CLAUDINO, Rinaldo; MARQUES, Wilson. Genetic epidemiology of familial ALS in Brazil. Neurobiology Of Aging, [S.L.], v. 102, p. 227-227, jun. 2021. Elsevier BV. http://dx.doi.org/10.1016/j.neurobiolaging.2021.01.007. Disponível em: https://www.sciencedirect.com/science/article/pii/S0197458021000142?via%3Dihub. Acesso em: 13 jul. 2023. |
url |
https://repositorio.ufrn.br/handle/123456789/54159 https://doi.org/10.1016/j.neurobiolaging.2021.01.007 |
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