Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain

This article belongs to the Special Issue Genetic Advances in Neuromuscular Disorders: From Gene Identification to Gene Therapy.

Detalles Bibliográficos
Autores: González-Quereda, Lidia, Rodríguez, María José, Díaz-Manera, Jordi, Alonso-Pérez, Jorge, Gallardo, Eduard, Nascimento, Andrés, Ortez, Carlos, Natera-de Benito, Daniel, Olivé, Montse, González-Mera, Laura, López de Munain, Adolfo, Zulaica, Miren, Poza, Juan José, Jericó, Ivonne, Torne, Laura, Riera, Pau, Milisenda, José, Sánchez, Aurora, Garrabou, Glòria, Llano, Isabel, Madruga, Marcos, Gallano, Pia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/235431
Acceso en línea:http://hdl.handle.net/10261/235431
Access Level:acceso abierto
Palabra clave:Neuromuscular diseases
Congenital myopathies
Muscular dystrophies
Congenital myasthenic syndromes
Targeted next-generation sequencing
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spelling Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in SpainGonzález-Quereda, LidiaRodríguez, María JoséDíaz-Manera, JordiAlonso-Pérez, JorgeGallardo, EduardNascimento, AndrésOrtez, CarlosNatera-de Benito, DanielOlivé, MontseGonzález-Mera, LauraLópez de Munain, AdolfoZulaica, MirenPoza, Juan JoséJericó, IvonneTorne, LauraRiera, PauMilisenda, JoséSánchez, AuroraGarrabou, GlòriaLlano, IsabelMadruga, MarcosGallano, PiaNeuromuscular diseasesCongenital myopathiesMuscular dystrophiesCongenital myasthenic syndromesTargeted next-generation sequencingThis article belongs to the Special Issue Genetic Advances in Neuromuscular Disorders: From Gene Identification to Gene Therapy.The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients’ clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier.This study was granted by FIS PI15/01898, funded by ISCIII and FEDER, ‘Una manera de hacer Europa’ and by Fundación Mutua Madrileña in the “Convocatoria de ayudas a la Investigación en Salud 2015”. It was also funded by an ACCI grant from CIBERER. Daniel Natera-de Benito is the recipient of a grant from the Instituto de Salud Carlos III (Contrato Rio Hortega, CM17/00044).Multidisciplinary Digital Publishing InstituteInstituto de Salud Carlos IIIEuropean CommissionFundación Mutua MadrileñaCentro de Investigación Biomédica en Red Enfermedades Raras (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/235431reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://doi.org/10.3390/genes11050539Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2354312026-05-22T06:33:51Z
dc.title.none.fl_str_mv Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain
title Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain
spellingShingle Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain
González-Quereda, Lidia
Neuromuscular diseases
Congenital myopathies
Muscular dystrophies
Congenital myasthenic syndromes
Targeted next-generation sequencing
title_short Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain
title_full Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain
title_fullStr Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain
title_full_unstemmed Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain
title_sort Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain
dc.creator.none.fl_str_mv González-Quereda, Lidia
Rodríguez, María José
Díaz-Manera, Jordi
Alonso-Pérez, Jorge
Gallardo, Eduard
Nascimento, Andrés
Ortez, Carlos
Natera-de Benito, Daniel
Olivé, Montse
González-Mera, Laura
López de Munain, Adolfo
Zulaica, Miren
Poza, Juan José
Jericó, Ivonne
Torne, Laura
Riera, Pau
Milisenda, José
Sánchez, Aurora
Garrabou, Glòria
Llano, Isabel
Madruga, Marcos
Gallano, Pia
author González-Quereda, Lidia
author_facet González-Quereda, Lidia
Rodríguez, María José
Díaz-Manera, Jordi
Alonso-Pérez, Jorge
Gallardo, Eduard
Nascimento, Andrés
Ortez, Carlos
Natera-de Benito, Daniel
Olivé, Montse
González-Mera, Laura
López de Munain, Adolfo
Zulaica, Miren
Poza, Juan José
Jericó, Ivonne
Torne, Laura
Riera, Pau
Milisenda, José
Sánchez, Aurora
Garrabou, Glòria
Llano, Isabel
Madruga, Marcos
Gallano, Pia
author_role author
author2 Rodríguez, María José
Díaz-Manera, Jordi
Alonso-Pérez, Jorge
Gallardo, Eduard
Nascimento, Andrés
Ortez, Carlos
Natera-de Benito, Daniel
Olivé, Montse
González-Mera, Laura
López de Munain, Adolfo
Zulaica, Miren
Poza, Juan José
Jericó, Ivonne
Torne, Laura
Riera, Pau
Milisenda, José
Sánchez, Aurora
Garrabou, Glòria
Llano, Isabel
Madruga, Marcos
Gallano, Pia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
European Commission
Fundación Mutua Madrileña
Centro de Investigación Biomédica en Red Enfermedades Raras (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Neuromuscular diseases
Congenital myopathies
Muscular dystrophies
Congenital myasthenic syndromes
Targeted next-generation sequencing
topic Neuromuscular diseases
Congenital myopathies
Muscular dystrophies
Congenital myasthenic syndromes
Targeted next-generation sequencing
description This article belongs to the Special Issue Genetic Advances in Neuromuscular Disorders: From Gene Identification to Gene Therapy.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/235431
url http://hdl.handle.net/10261/235431
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://doi.org/10.3390/genes11050539
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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