{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:41:55Z","timestamp":1774316515271,"version":"3.50.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the <jats:italic>COLQ<\/jats:italic> gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within <jats:italic>COLQ<\/jats:italic> in two unrelated children with CMS. An intronic variant (c.393+1G&amp;gt;A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the <jats:italic>COLQ<\/jats:italic> and <jats:italic>AChE<\/jats:italic> gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A&amp;gt;C (p.Q381P). The splicing mutation c.393+1G&amp;gt;A was found to affect the normal splicing of <jats:italic>COLQ<\/jats:italic> exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A&amp;gt;C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of <jats:italic>COLQ<\/jats:italic> exons 14\u201315 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. <jats:italic>COLQ<\/jats:italic> expression was significantly lower in the probands than in the probands' parents and siblings, while <jats:italic>AChE<\/jats:italic> expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G&amp;gt;A, missense mutation c.1A&amp;gt;C (p.Q381P), and <jats:italic>COLQ<\/jats:italic> exon 14\u201315 deletion could cause CMS.<\/jats:p>","DOI":"10.3389\/fped.2021.679342","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T14:11:28Z","timestamp":1638367888000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene"],"prefix":"10.3389","volume":"9","author":[{"given":"Xiaona","family":"Luo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunmei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longlong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengnan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Lan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quanmei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongrong","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyi","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanfeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaming","family":"Xi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingbin","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanyi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yucai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/S1474-4422(14)70201-7","article-title":"Congenital 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lamina","volume":"133","author":"Arredondo","year":"2014","journal-title":"Hum Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1523\/JNEUROSCI.4374-09.2010","article-title":"ColQ controls postsynaptic differentiation at the neuromuscular junction","volume":"30","author":"Sigoillot","year":"2010","journal-title":"J Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.1096\/fj.201500162","article-title":"Neuromuscular junction immaturity and muscle atrophy are hallmarks of the ColQ-deficient mouse, a model of congenital myasthenic syndrome with acetylcholinesterase deficiency","volume":"30","author":"Sigoillot","year":"2016","journal-title":"FASE BJ."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1476","DOI":"10.1111\/j.1432-1033.2004.04052.x","article-title":"Elements of the C-terminal t peptide of acetylcholinesterase that determine amphiphilicity, homomeric and heteromeric associations, secretion and degradation","volume":"271","author":"Belbeoc'h","year":"2004","journal-title":"Eur J Biochem"},{"key":"B8","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/s0960-8966(02)00243-2","article-title":"Two novel mutations in the COLQ gene cause endplate acetylcholinesterase deficiency","volume":"13","author":"Ishigaki","year":"2003","journal-title":"Neuromuscul Disord."},{"key":"B9","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.pediatrneurol.2014.03.012","article-title":"Clinical and molecular analysis of a novel COLQ missense mutation causing congenital myasthenic syndrome in a Syrian family","volume":"51","author":"Matlik","year":"2014","journal-title":"Pediatr Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e117","DOI":"10.1212\/NXG.0000000000000117","article-title":"Copy number analysis reveals a novel multiexon deletion of the COLQ gene in congenital myasthenia","volume":"2","author":"Wang","year":"2016","journal-title":"Neurol 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