{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T03:52:20Z","timestamp":1782964340563,"version":"3.54.5"},"reference-count":17,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T00:00:00Z","timestamp":1586131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100003157","name":"Myasthenia Gravis Foundation of America","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003157","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Defects in the gene encoding synaptotagmin 2 <jats:italic>(SYT2)<\/jats:italic> have been linked to a presynaptic congenital myasthenic syndrome (CMS) and motor neuropathies. However, to date only dominant forms of the disease have been described. We report here a consanguineous patient with a severe recessive form of presynaptic CMS and denervation atrophy caused by the homozygous mutation c.1191delG, p.Arg397Serfs*37 in <jats:italic>SYT2<\/jats:italic>. The affected 2\u2010year\u2010old girl had profound weakness and areflexia with moderate bulbar deficit. Repetitive nerve stimulation revealed an extreme reduction of compound muscle action potential amplitudes at rest, with a striking facilitation followed by a progressive decline at fast stimulation rates. These findings were reminiscent, but not identical to those seen in the Lambert\u2013Eaton myasthenic syndrome. 3,4 diaminopyridine and pyridostigmine were effective to ameliorate muscle fatigue, but albuterol was ineffective. Modeling of the mutation using the rat Syt1 C2B x\u2010ray structure revealed that Arg397Serfs*37 disrupts a highly conserved amino acid sequence at the bottom face of the C2B domain not directly involved in calcium binding, but crucial for synaptotagmin\u2010SNARE interaction and exocytosis. Thus, this report describes a recessive form of synaptotagmin 2\u2010CMS and highlights the importance of the synaptotagmin C\u2010terminal on synaptic vesicle fusion and exocytosis.<\/jats:p>","DOI":"10.1002\/ajmg.a.61579","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T13:44:20Z","timestamp":1586180660000},"page":"1744-1749","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Recessive congenital myasthenic syndrome caused by a homozygous mutation in <scp><i>SYT2<\/i><\/scp> altering a highly conserved C\u2010terminal amino acid sequence"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0918-0760","authenticated-orcid":false,"given":"Ricardo A.","family":"Maselli","sequence":"first","affiliation":[{"name":"Department of Neurology University of California Davis  Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"H\u00e9lio","family":"van der Linden","sequence":"additional","affiliation":[{"name":"Rehabilitation Center Dr. Henrique Santillo  Goi\u00e2nia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ferns","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology University of California Davis  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.04832604"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13539"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00548-7"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.260491197"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.08.007"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02346379"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0021-9258(18)52479-0","article-title":"Structural and functional conservation of synaptotagmin (p65) in Drosophila and humans","volume":"266","author":"Perin M. 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