{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:32:45Z","timestamp":1790839965553,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The diagnosis of uncommon pediatric neuromuscular disease (NMD) is challenging due to genetic and phenotypic heterogeneity, yet is important to guide treatment, prognosis, and recurrence risk. Patients with diagnostically challenging presentations typically undergo extensive testing with variable molecular diagnostic yield. Given the advancement in next generation sequencing (NGS), we investigated the value of clinical whole exome sequencing (ES) in uncommon pediatric NMD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective cohort study of 106 pediatric NMD patients with a combination of ES, chromosomal microarray (CMA), and candidate gene testing was completed at a large tertiary referral center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A molecular diagnosis was achieved in 37\/79 (46%) patients with ES, 4\/44 (9%) patients with CMA, and 15\/74 (20%) patients with candidate gene testing. In 2\/79 (3%) patients, a dual molecular diagnosis explaining the neuromuscular disease process was identified. A total of 42 patients (53%) who received ES remained without a molecular diagnosis at the conclusion of the study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Due to NGS, molecular diagnostic yield of rare neurological diseases is at an all\u2010time high. We show that ES has a higher diagnostic rate compared to other genetic tests in a complex pediatric neuromuscular disease cohort and should be considered early in the diagnostic journey for select NMD patients with challenging presentations in which a clinical diagnosis is not evident.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27112","type":"journal-article","created":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T17:38:24Z","timestamp":1604511504000},"page":"304-310","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Clinical exome sequencing in the diagnosis of pediatric neuromuscular disease"],"prefix":"10.1002","volume":"63","author":[{"given":"Isabella","family":"Herman","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Section of Pediatric Neurology and Developmental Neuroscience Baylor College of Medicine &amp; Texas Children\u02bcs Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3029-0761","authenticated-orcid":false,"given":"Michael A.","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neurology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2233-3423","authenticated-orcid":false,"given":"Dana","family":"Marafi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davut","family":"Pehlivan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Pediatric Neurology and Developmental Neuroscience Baylor College of Medicine &amp; Texas Children\u02bcs Hospital  Houston Texas USA"},{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Calame","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Pediatric Neurology and Developmental Neuroscience Baylor College of Medicine &amp; Texas Children\u02bcs Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farida","family":"Abid","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Pediatric Neurology and Developmental Neuroscience Baylor College of Medicine &amp; Texas Children\u02bcs Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy E.","family":"Lotze","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Pediatric Neurology and Developmental Neuroscience Baylor College of Medicine &amp; Texas Children\u02bcs Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12810"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/10408363.2012.658906"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002800"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38418"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2016.06.017"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008480-200012000-00006"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2018.10.003"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz131"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.2274"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13101"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24687"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2016.116"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1677734"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3233\/JND-180376"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2287-8"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-64076-5.00037-5"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/diseases4010002"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073816664836"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0554-6"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1516767"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84457"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.05.015"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.649"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182272"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.01.012"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal5209"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.119"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.08.009"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15824"},{"key":"e_1_2_9_32_1","first-page":"1","article-title":"Whole genome sequencing expands diagnostic utility and improves clinical management in pediatric medicine","volume":"15012","author":"Stavropoulos DJ","year":"2016","journal-title":"NPJ Genom Med"}],"container-title":["Muscle &amp; 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