2026-04-29T20:21:17Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/252842024-10-23T13:07:25Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16958col_20.500.12105_16961col_20.500.12105_16962col_20.500.12105_16968col_20.500.12105_16976col_20.500.12105_16974col_20.500.12105_16972
Repisalud author Gonzalez-Quereda, Lidia author Rodriguez, Maria Jose author Diaz-Manera, Jordi author Alonso-Perez, Jorge author Gallardo, Eduard author Nascimento, Andres author Ortez, Carlos author Natera-de Benito, Daniel author Olive, Montse author Gonzalez-Mera, Laura author Munain, Adolfo Lopez de author Zulaica, Miren author Poza, Juan Jose author Jerico, Ivonne author Torne, Laura author Riera, Pau author Milisenda, Jose author Sanchez, Aurora author Garrabou, Gloria author Llano, Isabel author Madruga-Garrido, Marcos author Gallano, Pia 2024-10-23T13:07:24Z 2024-10-23T13:07:24Z 2020-05-11 10.3390/genes11050539 2073-4425 Genes http://hdl.handle.net/10668/15561 32403337 https://hdl.handle.net/20.500.12105/25284 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. eng Congenital myasthenic syndromes Congenital myopathies Muscular dystrophies Neuromuscular diseases Targeted next-generation sequencing Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain. research article