{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:52:56Z","timestamp":1788317576385,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"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":"crossref","award":["MMH-E-115-13, MMH-E-114-13, MMH-MM-113-13, MMH-E-113-13, MMH-MM-112-14, and MMH-E-112-13"],"award-info":[{"award-number":["MMH-E-115-13, MMH-E-114-13, MMH-MM-113-13, MMH-E-113-13, MMH-MM-112-14, and MMH-E-112-13"]}],"id":[{"id":"10.13039\/501100004861","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science and Technology Council, Taiwan","award":["NSTC-114-2811-B-195-002, NSTC-114-2314-B-195-001, NSTC-114-2314-B-715-001, NSTC-114-2314-B-195-002, NSTC-113-2314-B-195-003, NSTC-113-2314-B-195-004, NSTC-113-2314-B-715-002, NSTC-113-2314-B-195-021, NSTC-113-2811-B-195-001, NSTC-112-2314-B-195-014-MY3, NSTC-112-2811-B-195-001, and NSTC-112-2314-B-195-003"],"award-info":[{"award-number":["NSTC-114-2811-B-195-002, NSTC-114-2314-B-195-001, NSTC-114-2314-B-715-001, NSTC-114-2314-B-195-002, NSTC-113-2314-B-195-003, NSTC-113-2314-B-195-004, NSTC-113-2314-B-715-002, NSTC-113-2314-B-195-021, NSTC-113-2811-B-195-001, NSTC-112-2314-B-195-014-MY3, NSTC-112-2811-B-195-001, and NSTC-112-2314-B-195-003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Muscle biopsy has long been regarded as the cornerstone for diagnosing pediatric muscular disorders; however, it is invasive and may be limited by sampling error and inconclusive histopathological findings. This study aimed to evaluate whether whole-exome sequencing (WES) can effectively replace muscle biopsy as a first-line diagnostic approach in children with suspected neuromuscular disorders. Between January 2018 and December 2025, we prospectively enrolled 47 pediatric patients presenting with clinical features suggestive of muscular disorders at a tertiary medical center in Taiwan. The cohort included patients with suspected muscular dystrophies (n = 21), congenital myopathies (n = 23), and multiplex ligation-dependent probe amplification (MLPA)-negative Duchenne muscular dystrophy (DMD; n = 3). All patients underwent WES as the initial diagnostic test without prior muscle biopsy. Trio-based analysis using parental samples was performed in 29.8% of cases. Variant interpretation followed the American College of Medical Genetics and Genomics (ACMG) guidelines. WES identified a definitive molecular diagnosis in 72.3% of patients (34\/47). Diagnostic yields varied by subgroup: 100% (3\/3) in MLPA-negative DMD, 71.4% (15\/21) in muscular dystrophies, and 69.6% (16\/23) in congenital myopathies. Pathogenic or likely pathogenic variants were detected in 31 distinct genes, including COL6A1 and COL6A3, which are associated with Ullrich congenital muscular dystrophy. Notably, 58.8% of diagnosed patients (20\/34) received molecular diagnoses that differed from their initial clinical impression, encompassing conditions such as ZSWIM6-associated neurodevelopmental disorders, GJB2-related hearing loss, OCRL-associated Lowe syndrome, and various metabolic or syndromic disorders. In all three MLPA-negative DMD cases, WES identified point mutations amenable to mutation-specific therapies. No patient required a muscle biopsy for diagnostic confirmation during the study period. First-tier WES demonstrates high diagnostic utility in pediatric muscular disorders while avoiding invasive muscle biopsy. The high rate of diagnostic reclassification underscores the substantial phenotypic overlap between primary neuromuscular diseases and other neurological or systemic conditions. These findings support the early implementation of genetic testing to enable accurate diagnosis and timely initiation of targeted therapies.<\/jats:p>","DOI":"10.3390\/ijms27052446","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:25:59Z","timestamp":1772817959000},"page":"2446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Skipping the Biopsy: Real-World Experience of Whole-Exome Sequencing as First-Tier Testing in Pediatric Muscular Disorders"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8178-6938","authenticated-orcid":false,"given":"Chung-Lin","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital, Taipei 104217, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang-Ming Chiao-Tung University, Taipei 112304, Taiwan"},{"name":"International Rare Disease Center, MacKay Memorial Hospital, Taipei 104217, Taiwan"},{"name":"Department of Medicine, Mackay Medical University, New Taipei City 252005, Taiwan"},{"name":"Department of Nursing, Mackay Junior College of Medicine, Nursing and Management, New Taipei City 252005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hui","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital, Taipei 104217, Taiwan"},{"name":"International Rare Disease Center, MacKay Memorial Hospital, Taipei 104217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9776-2092","authenticated-orcid":false,"given":"Chih-Kuang","family":"Chuang","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei 104217, Taiwan"},{"name":"College of Medicine, Fu-Jen Catholic University, New Taipei City 242062, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei-Ching","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital, Taipei 104217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Rong","family":"Tu","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei 104217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Ting","family":"Lo","sequence":"additional","affiliation":[{"name":"International Rare Disease Center, MacKay Memorial Hospital, Taipei 104217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"International Rare Disease Center, MacKay Memorial Hospital, Taipei 104217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9619-0990","authenticated-orcid":false,"given":"Hsiang-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital, Taipei 104217, Taiwan"},{"name":"International Rare Disease Center, MacKay Memorial Hospital, Taipei 104217, Taiwan"},{"name":"Department of Medicine, Mackay Medical University, New Taipei City 252005, Taiwan"},{"name":"Department of Nursing, Mackay Junior College of Medicine, Nursing and Management, New Taipei City 252005, Taiwan"},{"name":"Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei 104217, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuan-Pei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, MacKay Memorial Hospital, Taipei 104217, Taiwan"},{"name":"International Rare Disease Center, MacKay Memorial Hospital, Taipei 104217, Taiwan"},{"name":"Department of Medicine, Mackay Medical University, New Taipei City 252005, Taiwan"},{"name":"Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei 104217, Taiwan"},{"name":"Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences, Taipei 112303, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.nmd.2023.12.007","article-title":"The 2024 version of the gene table of neuromuscular disorders (nuclear genome)","volume":"34","author":"Benarroch","year":"2024","journal-title":"Neuromuscul. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.3233\/JND-140045","article-title":"The epidemiology of neuromuscular disorders: A comprehensive overview of the literature","volume":"2","author":"Deenen","year":"2015","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1093\/brain\/awp236","article-title":"Prevalence of genetic muscle disease in Northern England: In-depth analysis of a muscle clinic population","volume":"132","author":"Norwood","year":"2009","journal-title":"Brain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1159\/000369343","article-title":"Prevalence of muscular dystrophies: A systematic literature review","volume":"43","author":"Theadom","year":"2014","journal-title":"Neuroepidemiology"},{"key":"ref_5","doi-asserted-by":"crossref","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":"ref_6","doi-asserted-by":"crossref","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":"ref_7","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.pmr.2012.06.006","article-title":"Muscle biopsy evaluation in neuromuscular disorders","volume":"23","author":"Joyce","year":"2012","journal-title":"Phys. Med. Rehabil. Clin. N. Am."},{"key":"ref_8","unstructured":"Dubowitz, V., Sewry, C.A., and Oldfors, A. (2021). Muscle Biopsy: A Practical Approach, Elsevier. [5th ed.]."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/dmcn.14365","article-title":"Congenital myopathies: An update","volume":"62","author":"Claeys","year":"2020","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/B978-0-444-59565-2.00004-6","article-title":"Congenital myopathies","volume":"113","author":"Romero","year":"2013","journal-title":"Handb. Clin. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/pan.12909","article-title":"Anesthetic management of 877 pediatric patients undergoing muscle biopsy for neuromuscular disorders: A 20-year review","volume":"26","author":"Shapiro","year":"2016","journal-title":"Paediatr. Anaesth."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/mus.26083","article-title":"Dystrophinopathy muscle biopsies in the genetic testing era: One center\u2019s data","volume":"58","author":"Carlson","year":"2018","journal-title":"Muscle Nerve"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Veneruso, M., Fiorillo, C., Broda, P., Baratto, S., Traverso, M., Donati, A., Savasta, S., Capponi, S., Garibaldi, M., and Bruno, C. (2021). The role of muscle biopsy in diagnostic process of infant hypotonia: From clinical classification to the genetic outcome. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.735488"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e12888","DOI":"10.1111\/nan.12888","article-title":"Muscle biopsy practices in the evaluation of neuromuscular disease: A systematic literature review","volume":"49","author":"Ross","year":"2023","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e212","DOI":"10.1212\/NXG.0000000000000212","article-title":"Diagnostic utility of exome sequencing in the evaluation of neuromuscular disorders","volume":"4","author":"Haskell","year":"2018","journal-title":"Neurol. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1097\/WCO.0000000000000371","article-title":"Next-generation sequencing approaches for the diagnosis of skeletal muscle disorders","volume":"29","author":"Nigro","year":"2016","journal-title":"Curr. Opin. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"241","DOI":"10.3233\/JND-180376","article-title":"Panel-based exome sequencing for neuromuscular disorders as a diagnostic service","volume":"6","author":"Westra","year":"2019","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nature08250","article-title":"Targeted capture and massively parallel sequencing of 12 human exomes","volume":"461","author":"Ng","year":"2009","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/jhg.2013.114","article-title":"The promise of whole-exome sequencing in medical genetics","volume":"59","author":"Rabbani","year":"2014","journal-title":"J. Hum. Genet."},{"key":"ref_20","unstructured":"Tsang, H.Y. (2022). Exome Sequencing in Paediatric Neurogenetic Diseases. [Ph.D. Thesis, University of Hong Kong]."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/mus.27112","article-title":"Clinical exome sequencing in the diagnosis of pediatric neuromuscular disease","volume":"63","author":"Herman","year":"2021","journal-title":"Muscle Nerve"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41525-017-0006-7","article-title":"Cost-effectiveness of massively parallel sequencing for diagnosis of paediatric muscle diseases","volume":"2","author":"Schofield","year":"2017","journal-title":"NPJ Genom. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3233\/JND-170231","article-title":"Early-onset myopathies: Clinical findings, prevalence of subgroups and diagnostic approach in a single neuromuscular referral center in Germany","volume":"4","author":"Vill","year":"2017","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1038\/s41390-025-04160-4","article-title":"Next-generation sequencing for pediatric-onset neuromuscular disorders unresolved by conventional diagnostic methods","volume":"98","author":"Kulsirichawaroj","year":"2025","journal-title":"Pediatr. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/mus.27976","article-title":"Exome sequencing in the pediatric neuromuscular clinic leads to more frequent diagnosis of both neuromuscular and neurodevelopmental conditions","volume":"68","author":"Meyer","year":"2023","journal-title":"Muscle Nerve"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1007\/s10072-023-07210-z","article-title":"Utility of exome sequencing for the diagnosis of pediatric-onset neuromuscular diseases beyond diagnostic yield: A narrative review","volume":"45","author":"Morte","year":"2024","journal-title":"Neurol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/gim.2013.99","article-title":"The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders","volume":"16","author":"Shashi","year":"2014","journal-title":"Genet. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1038\/gim.2016.1","article-title":"A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders","volume":"18","author":"Stark","year":"2016","journal-title":"Genet. Med."},{"key":"ref_29","doi-asserted-by":"crossref","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":"ref_30","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/gim.2017.247","article-title":"Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature","volume":"20","author":"Schwarze","year":"2018","journal-title":"Genet. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1038\/s41436-021-01242-6","article-title":"Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: An evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG)","volume":"23","author":"Manickam","year":"2021","journal-title":"Genet. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1089\/nat.2017.0682","article-title":"Development of exon skipping therapies for Duchenne muscular dystrophy: A critical review and a perspective on the outstanding issues","volume":"27","author":"Straub","year":"2017","journal-title":"Nucleic Acid Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/S0140-6736(17)31611-2","article-title":"Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","volume":"390","author":"McDonald","year":"2017","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrneurol.2011.81","article-title":"The collagen VI-related myopathies: Muscle meets its matrix","volume":"7","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1177\/0883073812436605","article-title":"Consensus statement on standard of care for congenital myopathies","volume":"27","author":"Wang","year":"2012","journal-title":"J. Child Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1111\/ene.14616","article-title":"Whole-exome analyses of congenital muscular dystrophy and congenital myopathy patients from India reveal a wide spectrum of known and novel mutations","volume":"28","author":"Sanga","year":"2021","journal-title":"Eur. J. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"107271","DOI":"10.1016\/j.clineuro.2022.107271","article-title":"Congenital muscle dystrophies: Role of singleton whole exome sequencing in countries with limited resources","volume":"217","author":"Masri","year":"2022","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_38","doi-asserted-by":"crossref","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":"ref_39","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/mus.20586","article-title":"Entries in the Leiden Duchenne muscular dystrophy mutation database: An overview of mutation types and paradoxical cases that confirm the reading-frame rule","volume":"34","author":"Fokkema","year":"2006","journal-title":"Muscle Nerve"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/jhg.2010.49","article-title":"Mutation spectrum of the dystrophin gene in 442 Duchenne\/Becker muscular dystrophy cases from one Japanese referral center","volume":"55","author":"Takeshima","year":"2010","journal-title":"J. Hum. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1038\/s41431-021-00852-7","article-title":"Solving patients with rare diseases through programmatic reanalysis of genome-phenome data","volume":"29","author":"Matalonga","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"eaal5209","DOI":"10.1126\/scitranslmed.aal5209","article-title":"Improving genetic diagnosis in Mendelian disease with transcriptome sequencing","volume":"9","author":"Cummings","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_43","doi-asserted-by":"crossref","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":"ref_44","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.nmd.2013.12.011","article-title":"Diagnostic approach to the congenital muscular dystrophies","volume":"24","author":"Wang","year":"2014","journal-title":"Neuromuscul. Disord."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0387-7604(03)00066-4","article-title":"The floppy infant: Contribution of genetic and metabolic disorders","volume":"25","author":"Prasad","year":"2003","journal-title":"Brain Dev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/ejhg.2016.146","article-title":"Clinical exome sequencing: Results from 2819 samples reflecting 1000 families","volume":"25","author":"Trujillano","year":"2017","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/gim.2015.148","article-title":"Clinical application of whole-exome sequencing across clinical indications","volume":"18","author":"Retterer","year":"2016","journal-title":"Genet. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-021-00248-3","article-title":"Duchenne muscular dystrophy","volume":"7","author":"Duan","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_49","doi-asserted-by":"crossref","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":"ref_50","doi-asserted-by":"crossref","first-page":"341","DOI":"10.2217\/cer-2019-0171","article-title":"Safety and effectiveness of ataluren: Comparison of results from the STRIDE Registry and CINRG DMD Natural History Study","volume":"9","author":"Mercuri","year":"2020","journal-title":"J. Comp. Eff. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/B978-0-08-045031-5.00005-0","article-title":"The collagen VI-related myopathies Ullrich congenital muscular dystrophy and Bethlem myopathy","volume":"101","year":"2011","journal-title":"Handb. Clin. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev-genom-091212-153523","article-title":"The RASopathies","volume":"14","author":"Rauen","year":"2013","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"R123","DOI":"10.1093\/hmg\/ddw191","article-title":"Pathogenetics of the RASopathies","volume":"25","author":"Tidyman","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ajhg.2014.07.008","article-title":"Exome sequencing identifies a recurrent de novo ZSWIM6 mutation associated with acromelic frontonasal dysostosis","volume":"95","author":"Smith","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_55","doi-asserted-by":"crossref","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":"ref_56","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/gim.2016.88","article-title":"Systematic reanalysis of clinical exome data yields additional diagnoses: Implications for providers","volume":"19","author":"Wenger","year":"2017","journal-title":"Genet. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1056\/NEJMc1812033","article-title":"Reanalysis of clinical exome sequencing data","volume":"380","author":"Liu","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","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. USA"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Mantere, T., Kersten, S., and Hoischen, A. (2019). Long-read sequencing emerging in medical genetics. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00426"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"15824","DOI":"10.1038\/ncomms15824","article-title":"Genetic diagnosis of Mendelian disorders via RNA sequencing","volume":"8","author":"Kremer","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/humu.22844","article-title":"GeneMatcher: A matching tool for connecting investigators with an interest in the same gene","volume":"36","author":"Sobreira","year":"2015","journal-title":"Hum. Mutat."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2446\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T05:13:09Z","timestamp":1772946789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,6]]},"references-count":61,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27052446"],"URL":"https:\/\/doi.org\/10.3390\/ijms27052446","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,6]]}}}