{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:01:53Z","timestamp":1779930113182,"version":"3.53.1"},"reference-count":13,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"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":["J Peripheral Nervous Sys"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report the case of a patient with a clinical phenotype characterized by distal lower limb weakness and pes cavus. The electrophysiological study showed slightly reduced or normal amplitude of motor potentials, a decremental response to repetitive nerve stimulation and post\u2010exercise facilitation. Muscle biopsy showed only mild neurogenic features. Genetic analysis included a clinical exome sequencing, followed by Sanger analysis. Three\u2010dimensional (3D) models were generated with a SwissModel (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/swissmodel.expasy.org\/\">https:\/\/swissmodel.expasy.org\/<\/jats:ext-link>) to explain the clinical observations and reinforce the pathogenic nature of the genetic variant identified. Genetic analysis demonstrated a new <jats:italic>de novo<\/jats:italic> heterozygous in frame deletion of the <jats:italic>SYT2<\/jats:italic> gene (NM_177402.4: c.1082_1096del), confirmed by Sanger sequencing, which removes five aminoacids in the C2B domain of synaptotagmin\u20102 protein, that cause a profound effect on the structure and function of this synaptic vesicle protein. We identified a <jats:italic>de novo<\/jats:italic> genetic variant in the <jats:italic>SYT2<\/jats:italic> gene, further supporting its association with a highly stereotyped clinical and electrophysiological phenotype. Our case showed electrophysiological features consistent with a presynaptic dysfunction in the neuromuscular junction with normal post\u2010exercise amplitudes, not supporting the presence of predominant axonal damage. Although the analysis of <jats:italic>SYT2<\/jats:italic> gene should be included in genetic analysis of patients presenting with this clinical phenotype that mimics motor neuropathy, clinicians have to consider the study of neuromuscular transmission to early identify this potentially treatable condition.<\/jats:p>","DOI":"10.1111\/jns.12425","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T23:59:55Z","timestamp":1608076795000},"page":"113-117","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A new <i>de novo SYT2<\/i> mutation presenting as distal weakness. Neuropathy or neuromuscular junction dysfunction?"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8813-2272","authenticated-orcid":false,"given":"Laura","family":"Fionda","sequence":"first","affiliation":[{"name":"Neuromuscular and Rare Disease Center, Department of Neuroscience Mental Health and Sensory Organs (NESMOS), Sant'Andrea Hospital, Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina","family":"Turon\u2010Sans","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital de la Santa Creu i Sant Pau, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras CIBERER  IICS\u2010Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Fuentes Prior","sequence":"additional","affiliation":[{"name":"Biomedical Research Institute (IIB) Molecular Bases of Disease Hospital de la Santa Creu i Sant Pau  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bernal Noguera","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras CIBERER  IICS\u2010Madrid Spain"},{"name":"Biomedical Research Institute (IIB) Molecular Bases of Disease Hospital de la Santa Creu i Sant Pau  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1428-1072","authenticated-orcid":false,"given":"Elena","family":"Cort\u00e9s\u2010Vicente","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital de la Santa Creu i Sant Pau, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras CIBERER  IICS\u2010Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Angeles","family":"L\u00f3pez\u2010P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital San Pedro  Logro\u00f1o Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Gallardo","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital de la Santa Creu i Sant Pau, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras CIBERER  IICS\u2010Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1411-5573","authenticated-orcid":false,"given":"Ricard","family":"Rojas\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Unit, Department of Neurology Hospital de la Santa Creu i Sant Pau, Universitat Aut\u00f2noma de 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