{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:28Z","timestamp":1787028448148,"version":"build-2736575974"},"reference-count":83,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T00:00:00Z","timestamp":1618876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["DTS16\/00196"],"award-info":[{"award-number":["DTS16\/00196"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["R\u00edo Hortega Grant CM17\/00054"],"award-info":[{"award-number":["R\u00edo Hortega Grant CM17\/00054"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["SLT002\/16\/00174, 2015 FEDER\/S-21, SLT002\/16\/00306"],"award-info":[{"award-number":["SLT002\/16\/00174, 2015 FEDER\/S-21, SLT002\/16\/00306"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Isabel Gemio, Madrid, Spain","award":["NeuroPaisaje"],"award-info":[{"award-number":["NeuroPaisaje"]}]},{"name":"RAC1 i Torrons Vicens","award":["Torr\u00f3 Solidari"],"award-info":[{"award-number":["Torr\u00f3 Solidari"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The diagnosis of neuromuscular diseases (NMDs) has been progressively evolving from the grouping of clinical symptoms and signs towards the molecular definition. Optimal clinical, biochemical, electrophysiological, electrophysiological, and histopathological characterization is very helpful to achieve molecular diagnosis, which is essential for establishing prognosis, treatment and genetic counselling. Currently, the genetic approach includes both the gene-targeted analysis in specific clinically recognizable diseases, as well as genomic analysis based on next-generation sequencing, analyzing either the clinical exome\/genome or the whole exome or genome. However, as of today, there are still many patients in whom the causative genetic variant cannot be definitely established and variants of uncertain significance are often found. In this review, we address these drawbacks by incorporating two additional biological omics approaches into the molecular diagnostic process of NMDs. First, functional genomics by introducing experimental cell and molecular biology to analyze and validate the variant for its biological effect in an in-house translational diagnostic program, and second, incorporating a multi-omics approach including RNA-seq, metabolomics, and proteomics in the molecular diagnosis of neuromuscular disease. Both translational diagnostics programs and omics are being implemented as part of the diagnostic process in academic centers and referral hospitals and, therefore, an increase in the proportion of neuromuscular patients with a molecular diagnosis is expected. This improvement in the process and diagnostic performance of patients will allow solving aspects of their health problems in a precise way and will allow them and their families to take a step forward in their lives.<\/jats:p>","DOI":"10.3390\/ijms22084274","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T13:58:04Z","timestamp":1618927084000},"page":"4274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Increasing Impact of Translational Research in the Molecular Diagnostics of Neuromuscular Diseases"],"prefix":"10.3390","volume":"22","author":[{"given":"D\u00e8lia","family":"Yubero","sequence":"first","affiliation":[{"name":"Department of Genetic and Molecular Medicine\u2014IPER, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-2085","authenticated-orcid":false,"given":"Daniel","family":"Natera-de Benito","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit, Department of Pediatric Neurology, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0350-6376","authenticated-orcid":false,"given":"Jordi","family":"Pijuan","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics and Molecular Medicine\u2014IPER, Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0588-9307","authenticated-orcid":false,"given":"Judith","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Genetic and Molecular Medicine\u2014IPER, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreto","family":"Martorell","sequence":"additional","affiliation":[{"name":"Department of Genetic and Molecular Medicine\u2014IPER, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Laboratory of Neurogenetics and Molecular Medicine\u2014IPER, Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guerau","family":"Fern\u00e0ndez","sequence":"additional","affiliation":[{"name":"Department of Genetic and Molecular Medicine\u2014IPER, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Maynou","sequence":"additional","affiliation":[{"name":"Department of Genetic and Molecular Medicine\u2014IPER, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Jou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hospital Sant Joan de D\u00e9u, Pediatric Biobank for Research, Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f2nica","family":"Roldan","sequence":"additional","affiliation":[{"name":"Department of Genetic and Molecular Medicine\u2014IPER, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Confocal Microscopy and Cellular Imaging Unit, Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8187-8103","authenticated-orcid":false,"given":"Carlos","family":"Ortez","sequence":"additional","affiliation":[{"name":"Neuromuscular Unit, Department of Pediatric Neurology, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Division of Pediatrics, Clinic Institute of Medicine &amp; Dermatology, Hospital Cl\u00ednic, University of Barcelona School of Medicine and Health Sciences, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, 08950 Barcelona, Spain"},{"name":"Neuromuscular Unit, Department of Pediatric Neurology, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6790-6988","authenticated-orcid":false,"given":"Janet","family":"Hoenicka","sequence":"additional","affiliation":[{"name":"Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, 08950 Barcelona, Spain"},{"name":"Laboratory of Neurogenetics and Molecular Medicine\u2014IPER, Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8635-5421","authenticated-orcid":false,"given":"Francesc","family":"Palau","sequence":"additional","affiliation":[{"name":"Department of Genetic and Molecular Medicine\u2014IPER, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Center for Biomedical Research Network on Rare Diseases (CIBERER), ISCIII, 08950 Barcelona, Spain"},{"name":"Laboratory of Neurogenetics and Molecular Medicine\u2014IPER, Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Department of Pathology, Hospital Sant Joan de D\u00e9u, Pediatric Biobank for Research, Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3109\/10408363.2012.658906","article-title":"Genetics of neuromuscular disorders","volume":"49","author":"Laing","year":"2012","journal-title":"Crit. 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