Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HRE
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.17/3744 |
Resumo: | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with clinical and etiological heterogeneity and a complex genetic contribution. Clinical, neuropathological, and genetic evidence revealed that ALS and frontotemporal dementia (FTD) are in part of a single disease continuum. Genetic causes have been identified in sporadic (SALS) and familial patients (FALS) and the recurrent genetic factor underlying ALS and FTD is the C9orf72 hexanucleotide repeat expansion (HRE). However, in our population, the concomitance of ALS and FTD cannot be explained by C9orf72 HRE in many FALS and SALS cases. Our aim is to further understand the genetic basis of ALS in Portuguese patients. 34 patients with FALS or SALS-FTD, negative for C9orf72 HRE, were screened for rare variants in a panel of 29 relevant genes by next-generation sequencing. We detected 15 variants in 11 genes, one classified as pathogenic in TARDBP, two as likely pathogenic in TARDBP and PRPH, and the others as variants of unknown significance (VUS). Gene variants, including VUS, were found in 41.2% FALS patients and 40% SALS-FTD. In most patients, no potential pathogenic variants were found. Our results emphasize the need to enhance the efforts to unravel the genetic architecture of ALS-FTD. |
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Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HREC9orf72 ProteinDNA Repeat ExpansionHigh-Throughput Nucleotide SequencingHumansPortugalAmyotrophic Lateral SclerosisFrontotemporal DementiaNeurodegenerative DiseasesHDE GENAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with clinical and etiological heterogeneity and a complex genetic contribution. Clinical, neuropathological, and genetic evidence revealed that ALS and frontotemporal dementia (FTD) are in part of a single disease continuum. Genetic causes have been identified in sporadic (SALS) and familial patients (FALS) and the recurrent genetic factor underlying ALS and FTD is the C9orf72 hexanucleotide repeat expansion (HRE). However, in our population, the concomitance of ALS and FTD cannot be explained by C9orf72 HRE in many FALS and SALS cases. Our aim is to further understand the genetic basis of ALS in Portuguese patients. 34 patients with FALS or SALS-FTD, negative for C9orf72 HRE, were screened for rare variants in a panel of 29 relevant genes by next-generation sequencing. We detected 15 variants in 11 genes, one classified as pathogenic in TARDBP, two as likely pathogenic in TARDBP and PRPH, and the others as variants of unknown significance (VUS). Gene variants, including VUS, were found in 41.2% FALS patients and 40% SALS-FTD. In most patients, no potential pathogenic variants were found. Our results emphasize the need to enhance the efforts to unravel the genetic architecture of ALS-FTD.SpringerRepositório do Centro Hospitalar Universitário de Lisboa Central, EPEGromicho, MCoutinho, AMPronto-Laborinho, ACRaposeiro, RTavares, JAntunes, Dde Carvalho, M2021-06-23T14:45:06Z2020-122020-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/3744engJ Neurol. 2020;267(12):3578-359210.1007/s00415-020-10042-yinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-10T09:44:11Zoai:repositorio.chlc.min-saude.pt:10400.17/3744Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:21:03.873881Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HRE |
title |
Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HRE |
spellingShingle |
Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HRE Gromicho, M C9orf72 Protein DNA Repeat Expansion High-Throughput Nucleotide Sequencing Humans Portugal Amyotrophic Lateral Sclerosis Frontotemporal Dementia Neurodegenerative Diseases HDE GEN |
title_short |
Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HRE |
title_full |
Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HRE |
title_fullStr |
Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HRE |
title_full_unstemmed |
Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HRE |
title_sort |
Targeted Next-Generation Sequencing Study in Familial ALS-FTD Portuguese Patients Negative for C9orf72 HRE |
author |
Gromicho, M |
author_facet |
Gromicho, M Coutinho, AM Pronto-Laborinho, AC Raposeiro, R Tavares, J Antunes, D de Carvalho, M |
author_role |
author |
author2 |
Coutinho, AM Pronto-Laborinho, AC Raposeiro, R Tavares, J Antunes, D de Carvalho, M |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE |
dc.contributor.author.fl_str_mv |
Gromicho, M Coutinho, AM Pronto-Laborinho, AC Raposeiro, R Tavares, J Antunes, D de Carvalho, M |
dc.subject.por.fl_str_mv |
C9orf72 Protein DNA Repeat Expansion High-Throughput Nucleotide Sequencing Humans Portugal Amyotrophic Lateral Sclerosis Frontotemporal Dementia Neurodegenerative Diseases HDE GEN |
topic |
C9orf72 Protein DNA Repeat Expansion High-Throughput Nucleotide Sequencing Humans Portugal Amyotrophic Lateral Sclerosis Frontotemporal Dementia Neurodegenerative Diseases HDE GEN |
description |
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with clinical and etiological heterogeneity and a complex genetic contribution. Clinical, neuropathological, and genetic evidence revealed that ALS and frontotemporal dementia (FTD) are in part of a single disease continuum. Genetic causes have been identified in sporadic (SALS) and familial patients (FALS) and the recurrent genetic factor underlying ALS and FTD is the C9orf72 hexanucleotide repeat expansion (HRE). However, in our population, the concomitance of ALS and FTD cannot be explained by C9orf72 HRE in many FALS and SALS cases. Our aim is to further understand the genetic basis of ALS in Portuguese patients. 34 patients with FALS or SALS-FTD, negative for C9orf72 HRE, were screened for rare variants in a panel of 29 relevant genes by next-generation sequencing. We detected 15 variants in 11 genes, one classified as pathogenic in TARDBP, two as likely pathogenic in TARDBP and PRPH, and the others as variants of unknown significance (VUS). Gene variants, including VUS, were found in 41.2% FALS patients and 40% SALS-FTD. In most patients, no potential pathogenic variants were found. Our results emphasize the need to enhance the efforts to unravel the genetic architecture of ALS-FTD. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12 2020-12-01T00:00:00Z 2021-06-23T14:45:06Z |
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.uri.fl_str_mv |
http://hdl.handle.net/10400.17/3744 |
url |
http://hdl.handle.net/10400.17/3744 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
J Neurol. 2020;267(12):3578-3592 10.1007/s00415-020-10042-y |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Springer |
publisher.none.fl_str_mv |
Springer |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799131306561372160 |