Targeted next-generation sequencing in a large cohort of genetically undiagnosed patients with neuromuscular disorders in Spain
Gonzalez-Quereda, L (Institut d'Investigació Biomèdica Sant Pau)
Rodriguez, Maria Jose (Institut d'Investigació Biomèdica Sant Pau)
Diaz-Manera, Jordi (Institut d'Investigació Biomèdica Sant Pau)
Alonso-Pérez, Jorge (Institut d'Investigació Biomèdica Sant Pau)
Gallardo, Eduard (Institut d'Investigació Biomèdica Sant Pau)
Nascimento, Andres (Institut de Recerca Sant Joan de Déu)
Ortez González, Carlos Ignacio (Institut de Recerca Sant Joan de Déu)
Natera-De Benito, Daniel (Institut de Recerca Sant Joan de Déu)
Olive, Montse (Hospital Universitari de Bellvitge)
Gonzalez-Mera, Laura (Hospital de Viladecans)
de Munain, Adolfo Lopez (UPV-EHU)
Zulaica, Miren (Instituto de Salud Carlos III)
Poza, Juan Jose (Hospital de Donostia (Sant Sebastià, País Basc))
Jerico, Ivonne (Complejo Hospitalario de Navarra)
Torne, Laura (Instituto de Investigación Sanitaria de Navarra)
Riera, Pau (Institut d'Investigació Biomèdica Sant Pau)
Milisenda, José César (Hospital Clínic i Provincial de Barcelona)
Sanchez, Aurora (Hospital Clínic i Provincial de Barcelona)
Garrabou, Gloria (Hospital Clínic i Provincial de Barcelona)
Llano, Isabel (Osakidetza Basque Health Service)
Madruga-Garrido, Marcos (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Gallano, Pia (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad PI15/01898
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Congenital myasthenic syndromes ; Congenital myopathies ; Muscular dystrophies ; Neuromuscular diseases ; Targeted next-generation sequencing
Published in:	Genes, Vol. 11 Núm. 5 (may 2020) , p. 539, ISSN 2073-4425

DOI: 10.3390/genes11050539
PMID: 32403337

13 p, 749.5 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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