{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:20:17Z","timestamp":1791901217962,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8240063043"],"award-info":[{"award-number":["8240063043"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82230039"],"award-info":[{"award-number":["82230039"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U2005201"],"award-info":[{"award-number":["U2005201"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,7,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Congenital myasthenic syndromes (CMS) represent a heterogeneous group of inherited disorders resulting from mutations in genes that encode proteins essential for neuromuscular transmission. Among these, mutations in the collagen\u2010like tail subunit of asymmetric acetylcholinesterase (\n                    <jats:italic>COLQ<\/jats:italic>\n                    ) define a distinct subtype of CMS, necessitating specialized diagnostic and therapeutic strategies to improve patient outcomes. Herein, we analyzed five\n                    <jats:italic>COLQ\u2010<\/jats:italic>\n                    CMS patients, focusing on their clinical features, electrophysiologic findings, genetic characteristics, and therapeutic responses. All five patients exhibited limb\u2010girdle weakness, and two experienced acute respiratory insufficiency. The age of symptom onset ranged from 2 to 33\u2009years, with an average diagnostic delay of 14\u2009years. All patients exhibited a decremental response to repetitive nerve stimulation and myopathic features on electromyography. Using whole exome sequencing (WES), complemented by PCR\u2010based screening and reverse transcription\u2010PCR (RT\u2010PCR) to clarify deletion and splicing mutations, five variants of the\n                    <jats:italic>COLQ<\/jats:italic>\n                    gene were identified. These included two novel splicing mutations, c.393\u2009+\u20093A&gt;G and c.814_814\u2009+\u20092dup, which caused aberrant splicing and premature truncation. Additionally, we found the deletion of exon 14\u201315 of the\n                    <jats:italic>COLQ<\/jats:italic>\n                    gene in three patients. All patients received salbutamol, leading to significant alleviation of primary symptoms during treatment. In conclusion, our findings offer critical insights into the clinical diagnosis and management of\n                    <jats:italic>COLQ<\/jats:italic>\n                    \u2010CMS and highlight the importance of recognizing clinical heterogeneity, diagnostic delays, and early genetic diagnosis, which may ultimately assist clinicians in accurately identifying and effectively treating such conditions.\n                  <\/jats:p>","DOI":"10.1096\/fj.202501466r","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T10:20:19Z","timestamp":1753352419000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of Novel Splicing Mutations and a Recurrent Deletion in COLQ Congenital Myasthenic Syndrome"],"prefix":"10.1096","volume":"39","author":[{"given":"Yue","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongpei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9542-5698","authenticated-orcid":false,"given":"Kang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscience, and Fujian Key Laboratory of Molecular Neurology, Fujian Medical University  Fuzhou China"},{"name":"Department of Neurology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.4.603"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043730"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae124"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-018-0520-7"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2011.09.002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51346"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13520"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e19980"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm325"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000006478"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001952"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-022-02422-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2023.12.009"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad315"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000001300"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcad299"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000117"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11121519"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.679342"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100380070003"},{"key":"e_1_2_9_22_1","first-page":"667","article-title":"Non\u2010Homologous Recombination Between Alu and LINE\u20101 Repeats Results in a 91 kb Deletion in MERTK Causing Severe Retinitis Pigmentosa","volume":"24","author":"Jonsson F.","year":"2018","journal-title":"Molecular Vision"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0960-8966(02)00243-2"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2019.12.007"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2012.04.022"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.2010.03663.x"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2020.08.362"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/CND.0000000000000160"},{"key":"e_1_2_9_29_1","first-page":"428","article-title":"Further Delineation of Clinical and Molecular Characteristics of Congenital Myasthenic Syndromes in Indian Families","volume":"28","author":"Mishra S.","year":"2020","journal-title":"European Journal of Human Genetics"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200002)47:2<162::AID-ANA5>3.0.CO;2-Q"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.08.003"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000167132.35865.31"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1086\/302551"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202501466R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T23:10:57Z","timestamp":1761693057000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202501466R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,24]]},"references-count":32,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2025,7,31]]}},"alternative-id":["10.1096\/fj.202501466R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202501466r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,24]]},"assertion":[{"value":"2025-05-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70865"}}