González Quereda, LidiaRodríguez, Maria JoseDiaz Manera, JordiAlonso Pérez, JorgeGallardo, EduardNascimento, AndrésOrtez, Carlos IgnacioNatera de Benito, DanielOlivé i Plana, MontserratGonzález Mera, LauraLópez de Munain, AdolfoZulaica, MirenPoza, Juan JoséJerico, IvonneTome, LauraRiera, PauMilisenda, JoséSánchez, AuroraGarrabou Tornos, GlòriaLlano, IsabelMadruga Garrido, MarcosGallano, Pia2020-11-092020-11-092020-05-01https://hdl.handle.net/2445/171875The 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.13 p.application/pdfengcc by (c) González Quereda et al., 2020http://creativecommons.org/licenses/by/3.0/es/Malalties neuromuscularsMalalties muscularsNeuromuscular diseasesMuscular Diseasesinfo:eu-repo/semantics/article2020-11-03info:eu-repo/semantics/openAccess32403337