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Sorting Rare ALS Genetic Variants by Targeted Re-Sequencing Panel in Italian Patients: OPTN, VCP, and SQSTM1 Variants Account for 3% of Rare Genetic Forms

Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease due to motor neuron loss variably associated with frontotemporal dementia (FTD). Next generation sequencing technology revealed an increasing number of rare and novel genetic variants and interpretation of th...

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Autores principales: Pensato, Viviana, Magri, Stefania, Dalla Bella, Eleonora, Tannorella, Pierpaola, Bersano, Enrica, Sorarù, Gianni, Gatti, Marta, Ticozzi, Nicola, Taroni, Franco, Lauria, Giuseppe, Mariotti, Caterina, Gellera, Cinzia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073901/
https://www.ncbi.nlm.nih.gov/pubmed/32028661
http://dx.doi.org/10.3390/jcm9020412
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author Pensato, Viviana
Magri, Stefania
Dalla Bella, Eleonora
Tannorella, Pierpaola
Bersano, Enrica
Sorarù, Gianni
Gatti, Marta
Ticozzi, Nicola
Taroni, Franco
Lauria, Giuseppe
Mariotti, Caterina
Gellera, Cinzia
author_facet Pensato, Viviana
Magri, Stefania
Dalla Bella, Eleonora
Tannorella, Pierpaola
Bersano, Enrica
Sorarù, Gianni
Gatti, Marta
Ticozzi, Nicola
Taroni, Franco
Lauria, Giuseppe
Mariotti, Caterina
Gellera, Cinzia
author_sort Pensato, Viviana
collection PubMed
description Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease due to motor neuron loss variably associated with frontotemporal dementia (FTD). Next generation sequencing technology revealed an increasing number of rare and novel genetic variants and interpretation of their pathogenicity represents a major challange in the diagnosis of ALS. We selected 213 consecutive patients with sporadic or familial (16%) ALS, tested negative for SOD1, FUS, TARDBP, and C9orf72 mutations. To reveal rare forms of genetic ALS, we performed a comprehensive multi-gene panel screening including 46 genes associated with ALS, hereditary motor neuronopathies, spastic paraplegia, and FTD. Our study allowed the identification of pathogenic or likely pathogenic variants in 4.2% of patients. The genes with the highest percentage of pathogenic variants were OPTN (1%), VCP (1%) SQSTM1(1%), SETX (0.4%), FIG4 (0.4%), and GARS1 (0.4%) genes. We also found 49 novel or rare gene variants of unknown significance in 30 patients (14%), 44 unlikely pathogenic variants (39%), and 48 variants in ALS susceptibility genes. The results of our study suggest the screening of OPTN, VCP, and SQSTM1 genes in routine diagnostic investigations for both sporadic and familial cases, and confirm the importance of diagnosis and couselling for patients and their relative family members.
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spelling pubmed-70739012020-03-19 Sorting Rare ALS Genetic Variants by Targeted Re-Sequencing Panel in Italian Patients: OPTN, VCP, and SQSTM1 Variants Account for 3% of Rare Genetic Forms Pensato, Viviana Magri, Stefania Dalla Bella, Eleonora Tannorella, Pierpaola Bersano, Enrica Sorarù, Gianni Gatti, Marta Ticozzi, Nicola Taroni, Franco Lauria, Giuseppe Mariotti, Caterina Gellera, Cinzia J Clin Med Article Amyotrophic lateral sclerosis (ALS) is an adult-onset progressive neurodegenerative disease due to motor neuron loss variably associated with frontotemporal dementia (FTD). Next generation sequencing technology revealed an increasing number of rare and novel genetic variants and interpretation of their pathogenicity represents a major challange in the diagnosis of ALS. We selected 213 consecutive patients with sporadic or familial (16%) ALS, tested negative for SOD1, FUS, TARDBP, and C9orf72 mutations. To reveal rare forms of genetic ALS, we performed a comprehensive multi-gene panel screening including 46 genes associated with ALS, hereditary motor neuronopathies, spastic paraplegia, and FTD. Our study allowed the identification of pathogenic or likely pathogenic variants in 4.2% of patients. The genes with the highest percentage of pathogenic variants were OPTN (1%), VCP (1%) SQSTM1(1%), SETX (0.4%), FIG4 (0.4%), and GARS1 (0.4%) genes. We also found 49 novel or rare gene variants of unknown significance in 30 patients (14%), 44 unlikely pathogenic variants (39%), and 48 variants in ALS susceptibility genes. The results of our study suggest the screening of OPTN, VCP, and SQSTM1 genes in routine diagnostic investigations for both sporadic and familial cases, and confirm the importance of diagnosis and couselling for patients and their relative family members. MDPI 2020-02-03 /pmc/articles/PMC7073901/ /pubmed/32028661 http://dx.doi.org/10.3390/jcm9020412 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pensato, Viviana
Magri, Stefania
Dalla Bella, Eleonora
Tannorella, Pierpaola
Bersano, Enrica
Sorarù, Gianni
Gatti, Marta
Ticozzi, Nicola
Taroni, Franco
Lauria, Giuseppe
Mariotti, Caterina
Gellera, Cinzia
Sorting Rare ALS Genetic Variants by Targeted Re-Sequencing Panel in Italian Patients: OPTN, VCP, and SQSTM1 Variants Account for 3% of Rare Genetic Forms
title Sorting Rare ALS Genetic Variants by Targeted Re-Sequencing Panel in Italian Patients: OPTN, VCP, and SQSTM1 Variants Account for 3% of Rare Genetic Forms
title_full Sorting Rare ALS Genetic Variants by Targeted Re-Sequencing Panel in Italian Patients: OPTN, VCP, and SQSTM1 Variants Account for 3% of Rare Genetic Forms
title_fullStr Sorting Rare ALS Genetic Variants by Targeted Re-Sequencing Panel in Italian Patients: OPTN, VCP, and SQSTM1 Variants Account for 3% of Rare Genetic Forms
title_full_unstemmed Sorting Rare ALS Genetic Variants by Targeted Re-Sequencing Panel in Italian Patients: OPTN, VCP, and SQSTM1 Variants Account for 3% of Rare Genetic Forms
title_short Sorting Rare ALS Genetic Variants by Targeted Re-Sequencing Panel in Italian Patients: OPTN, VCP, and SQSTM1 Variants Account for 3% of Rare Genetic Forms
title_sort sorting rare als genetic variants by targeted re-sequencing panel in italian patients: optn, vcp, and sqstm1 variants account for 3% of rare genetic forms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073901/
https://www.ncbi.nlm.nih.gov/pubmed/32028661
http://dx.doi.org/10.3390/jcm9020412
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