%0 Journal Article
%A Gonzalez-Quereda, Lidia
%A Rodriguez, Maria Jose
%A Diaz-Manera, Jordi
%A Alonso-Perez, Jorge
%A Gallardo, Eduard
%A Nascimento, Andres
%A Ortez, Carlos
%A Natera-de Benito, Daniel
%A Olive, Montse
%A Gonzalez-Mera, Laura
%A Munain, Adolfo Lopez de
%A Zulaica, Miren
%A Poza, Juan Jose
%A Jerico, Ivonne
%A Torne, Laura
%A Riera, Pau
%A Milisenda, Jose
%A Sanchez, Aurora
%A Garrabou, Gloria
%A Llano, Isabel
%A Madruga-Garrido, Marcos
%A Gallano, Pia
%T Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain.
%D 2020
%U http://hdl.handle.net/10668/15561
%X 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.
%K congenital myasthenic syndromes
%K congenital myopathies
%K muscular dystrophies
%K neuromuscular diseases
%K targeted next-generation sequencing
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