Gonzalez-Quereda, LidiaRodriguez, Maria JoseDiaz-Manera, JordiAlonso-Perez, JorgeGallardo, EduardNascimento, AndresOrtez, CarlosNatera-de Benito, DanielOlive, MontseGonzalez-Mera, LauraMunain, Adolfo Lopez deZulaica, MirenPoza, Juan JoseJerico, IvonneTorne, LauraRiera, PauMilisenda, JoseSanchez, AuroraGarrabou, GloriaLlano, IsabelMadruga-Garrido, MarcosGallano, Pia2023-02-082023-02-082020-05-11http://hdl.handle.net/10668/15561The 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/congenital myasthenic syndromescongenital myopathiesmuscular dystrophiesneuromuscular diseasestargeted next-generation sequencingAdolescentAdultAgedChildChild, PreschoolDNA Mutational AnalysisFemaleGenetic Association StudiesHigh-Throughput Nucleotide SequencingHumansInfantInfant, NewbornMaleMiddle AgedMitochondrial DiseasesMuscular DiseasesMutationNeuromuscular DiseasesSpainYoung Adultresearch article32403337open access10.3390/genes110505392073-4425PMC7288461https://www.mdpi.com/2073-4425/11/5/539/pdf?version=1590648374https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288461/pdf