{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:49:48Z","timestamp":1777499388394,"version":"3.51.4"},"reference-count":73,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"funder Health Research Institute of Santiago de Compostela (IDIS)","award":["IN607B2021\/04"],"award-info":[{"award-number":["IN607B2021\/04"]}]},{"name":"MetabERN and GAIN (Axencia Galega de Inovaci\u00f3n)","award":["IN607B2021\/04"],"award-info":[{"award-number":["IN607B2021\/04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Neuromuscular diseases are genetically highly heterogeneous, and differential diagnosis can be challenging. Over a 3-year period, we prospectively analyzed 268 pediatric and adult patients with a suspected diagnosis of inherited neuromuscular disorder (INMD) using comprehensive gene-panel analysis and next-generation sequencing. The rate of diagnosis increased exponentially with the addition of genes to successive versions of the INMD panel, from 31% for the first iteration (278 genes) to 40% for the last (324 genes). The global mean diagnostic rate was 36% (97\/268 patients), with a diagnostic turnaround time of 4\u20136 weeks. Most diagnoses corresponded to muscular dystrophies\/myopathies (68.37%) and peripheral nerve diseases (22.45%). The most common causative genes, TTN, RYR1, and ANO5, accounted for almost 30% of the diagnosed cases. Finally, we evaluated the utility of the differential diagnosis tool Phenomizer, which established a correlation between the phenotype and molecular findings in 21% of the diagnosed patients. In summary, comprehensive gene-panel analysis of all genes implicated in neuromuscular diseases facilitates a rapid diagnosis and provides a high diagnostic yield.<\/jats:p>","DOI":"10.3390\/jcm11102750","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T21:46:53Z","timestamp":1652392013000},"page":"2750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Rapid Molecular Diagnosis of Genetically Inherited Neuromuscular Disorders Using Next-Generation Sequencing Technologies"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1431-4644","authenticated-orcid":false,"given":"Sofia","family":"Barbosa-Gouveia","sequence":"first","affiliation":[{"name":"Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IDIS-Health Research Institute of Santiago de Compostela, Santiago de Compostela University Clinical Hospital, European Reference Network for Hereditary Metabolic Disorders (MetabERN), 15704 Santiago de Compostela, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3167-5919","authenticated-orcid":false,"given":"Maria Eugenia","family":"V\u00e1zquez-Mosquera","sequence":"additional","affiliation":[{"name":"Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IDIS-Health Research Institute of Santiago de Compostela, Santiago de Compostela University Clinical Hospital, European Reference Network for Hereditary Metabolic Disorders (MetabERN), 15704 Santiago de Compostela, Spain"}]},{"given":"Emiliano","family":"Gonz\u00e1lez-Vioque","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Puerta de Hierro-Majadahonda University Hospital, 28222 Majadahonda, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3757-262X","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Hermida-Ameijeiras","sequence":"additional","affiliation":[{"name":"Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IDIS-Health Research Institute of Santiago de Compostela, Santiago de Compostela University Clinical Hospital, European Reference Network for Hereditary Metabolic Disorders (MetabERN), 15704 Santiago de Compostela, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4992-1305","authenticated-orcid":false,"given":"Paula","family":"S\u00e1nchez-Pintos","sequence":"additional","affiliation":[{"name":"Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IDIS-Health Research Institute of Santiago de Compostela, Santiago de Compostela University Clinical Hospital, European Reference Network for Hereditary Metabolic Disorders (MetabERN), 15704 Santiago de Compostela, Spain"}]},{"given":"Maria Jos\u00e9","family":"de Castro","sequence":"additional","affiliation":[{"name":"Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IDIS-Health Research Institute of Santiago de Compostela, Santiago de Compostela University Clinical Hospital, European Reference Network for Hereditary Metabolic Disorders (MetabERN), 15704 Santiago de Compostela, Spain"}]},{"given":"Soraya Ramiro","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"Genetics Department, Hospital Universitario de Getafe, 28905 Madrid, Spain"}]},{"given":"Bel\u00e9n","family":"Gil-Fournier","sequence":"additional","affiliation":[{"name":"Genetics Department, Hospital Universitario de Getafe, 28905 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5151-988X","authenticated-orcid":false,"given":"Cristina","family":"Dom\u00ednguez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit, Imas12 Research Institute, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain"},{"name":"Center for Biomedical Network Research On Rare Diseases (CIBERER), Instituto de Salud Carlos III, 28029 Madrid, Spain"}]},{"given":"Ana","family":"Camacho Salas","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Hospital Universitario 12 de Octubre, Complutense University of Madrid, 28041 Madrid, Spain"}]},{"given":"Luis","family":"Negr\u00e3o","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Unit, Neurology Service, Centro Hospitalar e Universit\u00e1rio de Coimbra, 3000-075 Coimbra, Portugal"}]},{"given":"Isabel","family":"Fineza","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Child Developmental Center, Hospital Pedi\u00e1trico, Centro Hospitalar e Universit\u00e1rio de Coimbra Coimbra Portugal, 3000-075 Coimbra, Portugal"}]},{"given":"Francisco","family":"Laranjeira","sequence":"additional","affiliation":[{"name":"Biochemical Genetics Unit, Centro de Gen\u00e9tica M\u00e9dica Doutor Jacinto Magalh\u00e3es, 4050-466 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4861-9905","authenticated-orcid":false,"given":"Maria Luz","family":"Couce","sequence":"additional","affiliation":[{"name":"Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Paediatrics, Santiago de Compostela University Clinical Hospital, 15704 Santiago de Compostela, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), IDIS-Health Research Institute of Santiago de Compostela, Santiago de Compostela University Clinical Hospital, European Reference Network for Hereditary Metabolic Disorders (MetabERN), 15704 Santiago de Compostela, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1097\/WCO.0000000000000478","article-title":"The Rapid Evolution of Molecular Genetic Diagnostics in Neuromuscular 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