RT Journal Article
T1 Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain.
A1 Gonzalez-Quereda, Lidia
A1 Rodriguez, Maria Jose
A1 Diaz-Manera, Jordi
A1 Alonso-Perez, Jorge
A1 Gallardo, Eduard
A1 Nascimento, Andres
A1 Ortez, Carlos
A1 Natera-de Benito, Daniel
A1 Olive, Montse
A1 Gonzalez-Mera, Laura
A1 Munain, Adolfo Lopez de
A1 Zulaica, Miren
A1 Poza, Juan Jose
A1 Jerico, Ivonne
A1 Torne, Laura
A1 Riera, Pau
A1 Milisenda, Jose
A1 Sanchez, Aurora
A1 Garrabou, Gloria
A1 Llano, Isabel
A1 Madruga-Garrido, Marcos
A1 Gallano, Pia
K1 congenital myasthenic syndromes
K1 congenital myopathies
K1 muscular dystrophies
K1 neuromuscular diseases
K1 targeted next-generation sequencing
AB 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.
YR 2020
FD 2020-05-11
LK http://hdl.handle.net/10668/15561
UL http://hdl.handle.net/10668/15561
LA en
DS RISalud
RD Apr 8, 2025