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Targeted sequencing panels in Italian ALS patients support different etiologies in the ALS/FTD continuum
BACKGROUND: 5–10% of amyotrophic lateral sclerosis (ALS) patients presented a positive family history (fALS). More than 30 genes have been identified in association with ALS/frontotemporal dementia (FTD) spectrum, with four major genes accounting for 60–70% of fALS. In this paper, we aimed to assess...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463338/ https://www.ncbi.nlm.nih.gov/pubmed/33770234 http://dx.doi.org/10.1007/s00415-021-10521-w |
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author | Bartoletti-Stella, Anna Vacchiano, Veria De Pasqua, Silvia Mengozzi, Giacomo De Biase, Dario Bartolomei, Ilaria Avoni, Patrizia Rizzo, Giovanni Parchi, Piero Donadio, Vincenzo Chiò, Adriano Pession, Annalisa Oppi, Federico Salvi, Fabrizio Liguori, Rocco Capellari, Sabina |
author_facet | Bartoletti-Stella, Anna Vacchiano, Veria De Pasqua, Silvia Mengozzi, Giacomo De Biase, Dario Bartolomei, Ilaria Avoni, Patrizia Rizzo, Giovanni Parchi, Piero Donadio, Vincenzo Chiò, Adriano Pession, Annalisa Oppi, Federico Salvi, Fabrizio Liguori, Rocco Capellari, Sabina |
author_sort | Bartoletti-Stella, Anna |
collection | PubMed |
description | BACKGROUND: 5–10% of amyotrophic lateral sclerosis (ALS) patients presented a positive family history (fALS). More than 30 genes have been identified in association with ALS/frontotemporal dementia (FTD) spectrum, with four major genes accounting for 60–70% of fALS. In this paper, we aimed to assess the contribution to the pathogenesis of major and rare ALS/FTD genes in ALS patients. METHODS: We analyzed ALS and ALS/FTD associated genes by direct sequencing or next-generation sequencing multigene panels in ALS patients. RESULTS: Genetic abnormalities in ALS major genes included repeated expansions of hexanucleotide in C9orf72 gene (7.3%), mutations in SOD1 (4.9%), FUS (2.1%), and TARDBP (2.4%), whereas variants in rare ALS/FTD genes affected 15.5% of subjects overall, most frequently involving SQSTM1 (3.4%), and CHMP2B (1.9%). We found clustering of variants in ALS major genes in patients with a family history for “pure” ALS, while ALS/FTD related genes mainly occurred in patients with a family history for other neurodegenerative diseases (dementia and/or parkinsonism). CONCLUSIONS: Our data support the presence of two different genetic components underlying ALS pathogenesis, related to the presence of a family history for ALS or other neurodegenerative diseases. Thus, family history may help in optimizing the genetic screening protocol to be applied. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-021-10521-w. |
format | Online Article Text |
id | pubmed-8463338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-84633382021-10-08 Targeted sequencing panels in Italian ALS patients support different etiologies in the ALS/FTD continuum Bartoletti-Stella, Anna Vacchiano, Veria De Pasqua, Silvia Mengozzi, Giacomo De Biase, Dario Bartolomei, Ilaria Avoni, Patrizia Rizzo, Giovanni Parchi, Piero Donadio, Vincenzo Chiò, Adriano Pession, Annalisa Oppi, Federico Salvi, Fabrizio Liguori, Rocco Capellari, Sabina J Neurol Original Communication BACKGROUND: 5–10% of amyotrophic lateral sclerosis (ALS) patients presented a positive family history (fALS). More than 30 genes have been identified in association with ALS/frontotemporal dementia (FTD) spectrum, with four major genes accounting for 60–70% of fALS. In this paper, we aimed to assess the contribution to the pathogenesis of major and rare ALS/FTD genes in ALS patients. METHODS: We analyzed ALS and ALS/FTD associated genes by direct sequencing or next-generation sequencing multigene panels in ALS patients. RESULTS: Genetic abnormalities in ALS major genes included repeated expansions of hexanucleotide in C9orf72 gene (7.3%), mutations in SOD1 (4.9%), FUS (2.1%), and TARDBP (2.4%), whereas variants in rare ALS/FTD genes affected 15.5% of subjects overall, most frequently involving SQSTM1 (3.4%), and CHMP2B (1.9%). We found clustering of variants in ALS major genes in patients with a family history for “pure” ALS, while ALS/FTD related genes mainly occurred in patients with a family history for other neurodegenerative diseases (dementia and/or parkinsonism). CONCLUSIONS: Our data support the presence of two different genetic components underlying ALS pathogenesis, related to the presence of a family history for ALS or other neurodegenerative diseases. Thus, family history may help in optimizing the genetic screening protocol to be applied. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-021-10521-w. Springer Berlin Heidelberg 2021-03-26 2021 /pmc/articles/PMC8463338/ /pubmed/33770234 http://dx.doi.org/10.1007/s00415-021-10521-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Communication Bartoletti-Stella, Anna Vacchiano, Veria De Pasqua, Silvia Mengozzi, Giacomo De Biase, Dario Bartolomei, Ilaria Avoni, Patrizia Rizzo, Giovanni Parchi, Piero Donadio, Vincenzo Chiò, Adriano Pession, Annalisa Oppi, Federico Salvi, Fabrizio Liguori, Rocco Capellari, Sabina Targeted sequencing panels in Italian ALS patients support different etiologies in the ALS/FTD continuum |
title | Targeted sequencing panels in Italian ALS patients support different etiologies in the ALS/FTD continuum |
title_full | Targeted sequencing panels in Italian ALS patients support different etiologies in the ALS/FTD continuum |
title_fullStr | Targeted sequencing panels in Italian ALS patients support different etiologies in the ALS/FTD continuum |
title_full_unstemmed | Targeted sequencing panels in Italian ALS patients support different etiologies in the ALS/FTD continuum |
title_short | Targeted sequencing panels in Italian ALS patients support different etiologies in the ALS/FTD continuum |
title_sort | targeted sequencing panels in italian als patients support different etiologies in the als/ftd continuum |
topic | Original Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463338/ https://www.ncbi.nlm.nih.gov/pubmed/33770234 http://dx.doi.org/10.1007/s00415-021-10521-w |
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