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

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 heterogen...

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Detalles Bibliográficos
Autores: González Quereda, Lidia, Rodríguez, Maria Jose, Diaz Manera, Jordi, Alonso Pérez, Jorge, Gallardo, Eduard, Nascimento, Andrés, Ortez, Carlos Ignacio, Natera de Benito, Daniel, Olivé i Plana, Montserrat, González Mera, Laura, López de Munain, Adolfo, Zulaica, Miren, Poza, Juan José, Jerico, Ivonne, Tome, Laura, Riera, Pau, Milisenda, José, Sánchez, Aurora, Garrabou Tornos, Glòria, Llano, Isabel, Madruga Garrido, Marcos, Gallano, Pia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/171875
Acceso en línea:https://hdl.handle.net/2445/171875
Access Level:acceso abierto
Palabra clave:Malalties neuromusculars
Malalties musculars
Neuromuscular diseases
Muscular Diseases
Descripción
Sumario: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 asTTN,NEBandRYR1.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.

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