{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T15:36:17Z","timestamp":1773502577805,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science London","doi-asserted-by":"publisher","award":["JP20H03561"],"award-info":[{"award-number":["JP20H03561"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009438","name":"National Center of Neurology and Psychiatry","doi-asserted-by":"publisher","award":["2\u20105"],"award-info":[{"award-number":["2\u20105"]}],"id":[{"id":"10.13039\/501100009438","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To dissect the kinetic defects of acetylcholine receptor (AChR) \u03b3 subunit variant in an incomplete form of the Escobar syndrome without pterygium and compare it with those of a variant of corresponding residue in the AChR \u03b5 subunit in a congenital myasthenic syndrome (CMS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole exome sequencing, \u03b1\u2010bungarotoxin binding assay, single channel patch\u2010clamp recordings, and maximum likelihood analysis of channel kinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified compound heterozygous variants in AChR \u03b3 and \u03b5 subunits in three Escobar syndrome (1\u20133) and three CMS patients (4\u20136), respectively. Each Escobar syndrome patient carries \u03b3P121R along with \u03b3V221Afs*44 in patients 1 and 2, and \u03b3Y63* in patient 3. Three CMS patients share \u03b5P121T along with \u03b5R20W, \u03b5G\u20108R, and \u03b5Y15H in patients 4, 5, and 6, respectively. Surface expressions of \u03b3P121R\u2010 and \u03b5P121T\u2010AChR were 80% and 138% of the corresponding wild\u2010type AChR, whereas \u03b5R20W, \u03b5G\u20108R, and \u03b5Y15H reduced receptor expression to 27%, 35%, and 30% of wild\u2010type \u03b5AChR, respectively. \u03b3V221Afs*44 and \u03b3Y63* are null variants. Thus, \u03b3P121R and \u03b5P121T determine the phenotype. \u03b3P121R and \u03b5P121T shorten channel opening burst duration to 28% and 18% of corresponding wild\u2010type AChR by reducing the channel gating equilibrium constant 44\u2010 and 63\u2010fold, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Similar impairment of channel gating efficiency of a corresponding P121 residue in the acetylcholine\u2010binding site of the AChR \u03b3 and <jats:italic>\u03b5<\/jats:italic> subunits causes Escobar syndrome without pterygium and fast\u2010channel CMS, respectively, suggesting that therapy for the fast\u2010channel CMS will benefit Escobar syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51756","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T09:25:23Z","timestamp":1678353923000},"page":"732-743","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Impaired gating of \u03b3\u2010 and <scp>\u03b5\u2010AChR<\/scp> respectively causes Escobar syndrome and fast\u2010channel myasthenia"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7087-5166","authenticated-orcid":false,"given":"Xin\u2010Ming","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Neurology and Neuromuscular Research Laboratory Mayo Clinic  Rochester Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiko","family":"Nakata","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics, Center for Neurological Diseases and Cancer Nagoya University 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