{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:17Z","timestamp":1787026517434,"version":"build-2736575974"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004861","name":"Mackay Memorial Hospital","doi-asserted-by":"publisher","award":["MMH-MM-112-14, MMH-E-112-13, and MMH-E-111-13"],"award-info":[{"award-number":["MMH-MM-112-14, MMH-E-112-13, and MMH-E-111-13"]}],"id":[{"id":"10.13039\/501100004861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Muscular dystrophies and congenital myopathies encompass various inherited muscular disorders that present diagnostic challenges due to clinical complexity and genetic heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study aimed to investigate the use of whole exome sequencing (WES) in diagnosing muscular disorders in pediatric patients in Taiwan. Out of 161 pediatric patients suspected to have genetic\/inherited myopathies, 115 received a molecular diagnosis through conventional tests, single gene testing, and gene panels. The remaining 46 patients were divided into three groups: Group 1 (multiplex ligation-dependent probe amplification\u2013negative Duchenne muscular dystrophy) with three patients (6.5%), Group 2 (various forms of muscular dystrophies) with 21 patients (45.7%), and Group 3 (congenital myopathies) with 22 patients (47.8%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>WES analysis of these groups found pathogenic variants in 100.0% (3\/3), 57.1% (12\/21), and 68.2% (15\/22) of patients in Groups 1 to 3, respectively. WES had a diagnostic yield of 65.2% (30 patients out of 46), detecting 30 pathogenic or potentially pathogenic variants across 28 genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>WES enables the diagnosis of rare diseases with symptoms and characteristics similar to congenital myopathies and muscular dystrophies, such as muscle weakness. Consequently, this approach facilitates targeted therapy implementation and appropriate genetic counseling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2024.1365729","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:59:51Z","timestamp":1715734791000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Application of whole exome sequencing in the diagnosis of muscular disorders: a study of Taiwanese pediatric patients"],"prefix":"10.3389","volume":"15","author":[{"given":"Chung-Lin","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Kuang","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei-Ching","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hui","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Rong","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ting","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiang-Yu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuan-Pei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.ajhg.2016.06.001","article-title":"Performance of ACMG-AMP variant-interpretation guidelines among nine laboratories in the clinical sequencing exploratory research consortium","volume":"99","author":"Amendola","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1002\/ana.24303","article-title":"A comprehensive genomic approach for neuromuscular diseases gives a high diagnostic yield","volume":"77","author":"Ankala","year":"2015","journal-title":"Ann. Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e0252953","DOI":"10.1371\/journal.pone.0252953","article-title":"Diagnostic yield of exome sequencing in myopathies: experience of a Slovenian tertiary centre","volume":"16","author":"Babic-Bozovic","year":"2021","journal-title":"PLoS One"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e241","DOI":"10.1371\/journal.pcbi.0030241","article-title":"Stereochemical criteria for prediction of the effects of proline mutations on protein stability","volume":"3","author":"Bajaj","year":"2007","journal-title":"PLoS Comput. Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"5473","DOI":"10.1073\/pnas.1418631112","article-title":"Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants","volume":"112","author":"Belkadi","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1016\/j.nmd.2020.11.009","article-title":"The 2021 version of the gene table of neuromuscular disorders (nuclear genome)","volume":"30","author":"Benarroch","year":"2020","journal-title":"Neuromuscul. Disord."},{"key":"B7","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S1474-4422(18)30024-3","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management","volume":"17","author":"Birnkrant","year":"2018","journal-title":"Lancet Neurol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e67527","DOI":"10.1371\/journal.pone.0067527","article-title":"An integrated diagnosis strategy for congenital myopathies","volume":"8","author":"B\u00f6hm","year":"2013","journal-title":"PLoS One"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1558","DOI":"10.1002\/humu.22429","article-title":"Position of glycine substitutions in the triple helix of COL6A1, COL6A2, and COL6A3 is correlated with severity and mode of inheritance in collagen VI myopathies","volume":"34","author":"Butterfield","year":"2013","journal-title":"Hum. Mutat."},{"key":"B10","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1136\/jmedgenet-2014-102819","article-title":"Utility of next generation sequencing in genetic diagnosis of early onset neuromuscular disorders","volume":"52","author":"Chae","year":"2015","journal-title":"J. Med. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1590\/0004-282X20170151","article-title":"The relative frequency of common neuromuscular diagnoses in a reference center","volume":"75","author":"Cotta","year":"2017","journal-title":"Arq. Neuropsiquiatr."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1001\/jama.2014.1717","article-title":"Clinical interpretation and implications of whole-genome sequencing","volume":"311","author":"Dewey","year":"2014","journal-title":"JAMA"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e1000183","DOI":"10.1371\/journal.pgen.1000183","article-title":"A catalog of neutral and deleterious polymorphism in yeast","volume":"4","author":"Doniger","year":"2008","journal-title":"PLoS Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1002\/ajmg.a.38418","article-title":"Treating pediatric neuromuscular disorders: the future is now","volume":"176","author":"Dowling","year":"2018","journal-title":"Am. J. Med. Genet. A"},{"key":"B15","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1006\/jmbi.2001.5255","article-title":"Characterization of disease-associated single amino acid polymorphisms in terms of sequence and structure properties","volume":"315","author":"Ferrer-Costa","year":"2002","journal-title":"J. Mol. Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13023-019-1025-5","article-title":"Congenital myasthenic syndromes","volume":"14","author":"Finsterer","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1002\/humu.21114","article-title":"Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort","volume":"30","author":"Flanigan","year":"2009","journal-title":"Hum. Mutat."},{"key":"B18","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/s41467-018-03133-y","article-title":"Identifying noncoding risk variants using disease-relevant gene regulatory networks","volume":"9","author":"Gao","year":"2018","journal-title":"Nat. Commun."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1001\/jamaneurol.2015.2274","article-title":"Use of whole-exome sequencing for diagnosis of limb-girdle muscular dystrophy: outcomes and lessons learned","volume":"72","author":"Ghaoui","year":"2015","journal-title":"JAMA Neurol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s13023-017-0699-9","article-title":"Exome sequences versus sequential gene testing in the UK highly specialised Service for Limb Girdle Muscular Dystrophy","volume":"12","author":"Harris","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1111\/epi.14087","article-title":"A population-based cost-effectiveness study of early genetic testing in severe epilepsies of infancy","volume":"59","author":"Howell","year":"2018","journal-title":"Epilepsia"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1212\/WNL.0000000000001416","article-title":"Evidence-based guideline summary: evaluation, diagnosis, and management of congenital muscular dystrophy: report of the guideline development subcommittee of the American academy of neurology and the practice issues review panel of the American association of neuromuscular & electrodiagnostic medicine","volume":"84","author":"Kang","year":"2015","journal-title":"Neurology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1136\/jmg.2002.002311","article-title":"Collagen VI related muscle disorders","volume":"42","author":"Lampe","year":"2005","journal-title":"J. Med. Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/j.nmd.2018.08.012","article-title":"Small mutation screening in the DMD gene by whole exome sequencing of an argentine Duchenne\/Becker muscular dystrophies cohort","volume":"28","author":"Luce","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"B25","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s00439-015-1631-9","article-title":"Clinical sequencing: is WGS the better WES?","volume":"135","author":"Meienberg","year":"2016","journal-title":"Hum. Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1016\/S0140-6736(19)32910-1","article-title":"Muscular dystrophies","volume":"394","author":"Mercuri","year":"2019","journal-title":"Lancet"},{"key":"B27","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1093\/hmg\/10.21.2319","article-title":"Understanding human disease mutations through the use of interspecific genetic variation","volume":"10","author":"Miller","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"B28","doi-asserted-by":"publisher","first-page":"7427","DOI":"10.1007\/s11033-023-08644-6","article-title":"Whole exome sequencing identifies a novel variant in the COL12A1 gene in a family with Ullrich congenital muscular dystrophy 2","volume":"50","author":"Naghipoor","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"E1687","DOI":"10.1002\/humu.21330","article-title":"Plectin deficiency leads to both muscular dystrophy and pyloric atresia in epidermolysis bullosa simplex","volume":"31","author":"Natsuga","year":"2010","journal-title":"Hum. Mutat."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3812","DOI":"10.1093\/nar\/gkg509","article-title":"SIFT: predicting amino acid changes that affect protein function","volume":"31","author":"Ng","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.nmd.2013.11.003","article-title":"Approach to the diagnosis of congenital myopathies","volume":"24","author":"North","year":"2014","journal-title":"Neuromuscul. Disord."},{"key":"B32","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/jhg.2016.7","article-title":"Genetic diagnosis of Duchenne\/Becker muscular dystrophy using next-generation sequencing: validation analysis of DMD mutations","volume":"61","author":"Okubo","year":"2016","journal-title":"J. Hum. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1186\/s13023-019-1227-x","article-title":"Epidemiological study and genetic characterization of inherited muscle diseases in a northern Spanish region","volume":"14","author":"Pagola-Lorz","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1016\/j.ajhg.2017.10.009","article-title":"A recurrent de novo nonsense variant in ZSWIM6 results in severe intellectual disability without frontonasal or limb malformations","volume":"101","author":"Palmer","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"B35","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1038\/jhg.2016.116","article-title":"The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States","volume":"62","author":"Reddy","year":"2017","journal-title":"J. Hum. Genet."},{"key":"B36","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of medical genetics and genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s10974-019-09519-9","article-title":"Nemaline myopathies: a current view","volume":"40","author":"Sewry","year":"2019","journal-title":"J. Muscle Res. Cell Motil."},{"key":"B38","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.nmd.2018.05.007","article-title":"229th ENMC international workshop: limb girdle muscular dystrophies - nomenclature and reformed classification Naarden, The Netherlands, 17-19 March 2017","volume":"28","author":"Straub","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"B39","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1001\/jamapediatrics.2017.1755","article-title":"Diagnostic impact and cost-effectiveness of whole-exome sequencing for ambulant children with suspected monogenic conditions","volume":"171","author":"Tan","year":"2017","journal-title":"JAMA Pediatr."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1038\/gim.2017.210","article-title":"Modeling the ACMG\/AMP variant classification guidelines as a Bayesian classification framework","volume":"20","author":"Tavtigian","year":"2018","journal-title":"Genet. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1212\/WNL.0000000000001783","article-title":"Evidence-based guideline summary: evaluation, diagnosis, and management of facioscapulohumeral muscular dystrophy: report of the guideline development, dissemination, and implementation subcommittee of the American academy of neurology and the practice issues review panel of the American association of neuromuscular & electrodiagnostic medicine","volume":"85","author":"Tawil","year":"2015","journal-title":"Neurology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s13023-015-0364-0","article-title":"Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth","volume":"10","author":"Todd","year":"2015","journal-title":"Orphanet J. Rare Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1002\/humu.20976","article-title":"Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase","volume":"30","author":"Tuffery-Giraud","year":"2009","journal-title":"Hum. Mutat."},{"key":"B44","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1111\/cge.12721","article-title":"Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism","volume":"90","author":"Twigg","year":"2016","journal-title":"Clin. Genet."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e53083","DOI":"10.1371\/journal.pone.0053083","article-title":"Comprehensive mutation analysis for congenital muscular dystrophy: a clinical PCR-based enrichment and next-generation sequencing panel","volume":"8","author":"Valencia","year":"2013","journal-title":"PLoS One"},{"key":"B46","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1055\/s-0039-1677734","article-title":"Diagnostic utility of whole exome sequencing in the neuromuscular clinic","volume":"50","author":"Waldrop","year":"2019","journal-title":"Neuropediatrics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s00401-012-1026-0","article-title":"The many faces of plectin and plectinopathies: pathology and mechanisms","volume":"125","author":"Winter","year":"2013","journal-title":"Acta Neuropathol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"e140","DOI":"10.1212\/NXG.0000000000000140","article-title":"Phenotypes, genotypes, and prevalence of congenital myopathies older than 5 years in Denmark","volume":"3","author":"Witting","year":"2017","journal-title":"Neurol. Genet."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2024.1365729\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T05:15:11Z","timestamp":1715836511000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2024.1365729\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,15]]},"references-count":48,"alternative-id":["10.3389\/fgene.2024.1365729"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2024.1365729","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,15]]},"article-number":"1365729"}}