{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:32:39Z","timestamp":1790260359731,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T00:00:00Z","timestamp":1685664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["GR\u20102016\u201002363337"],"award-info":[{"award-number":["GR\u20102016\u201002363337"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF\u20102019\u201012370491"],"award-info":[{"award-number":["RF\u20102019\u201012370491"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN 2017ALCR7C"],"award-info":[{"award-number":["PRIN 2017ALCR7C"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Variable phenotypes, including developmental encephalopathy with (DEE) or without seizures and myoclonic epilepsy and ataxia due to potassium channel mutation, are caused by pathogenetic variants in <jats:italic>KCNC1<\/jats:italic>, encoding for Kv3.1 channel subunits. In vitro, channels carrying most <jats:italic>KCNC1<\/jats:italic> pathogenic variants display loss\u2010of\u2010function features. Here, we describe a child affected by DEE with fever\u2010triggered seizures, caused by a novel de novo heterozygous missense <jats:italic>KCNC1<\/jats:italic> variant (c.1273G&gt;A; V425M). Patch\u2010clamp recordings in transiently transfected CHO cells revealed that, compared to wild\u2010type, Kv3.1 V425M currents (1) were larger, with membrane potentials between \u221240 and\u2009+40\u2009mV; (2) displayed a hyperpolarizing shift in activation gating; (3) failed to inactivate; and (4) had slower activation and deactivation kinetics, consistent with a mixed functional pattern with prevalent gain\u2010of\u2010function effects. Exposure to the antidepressant drug fluoxetine inhibited currents expressed by both wild\u2010type and mutant Kv3.1 channels. Treatment of the proband with fluoxetine led to a rapid and prolonged clinical amelioration, with the disappearance of seizures and an improvement in balance, gross motor skills, and oculomotor coordination. These results suggest that drug repurposing based on the specific genetic defect may provide an effective personalized treatment for <jats:italic>KCNC1<\/jats:italic>\u2010related DEEs.<\/jats:p>","DOI":"10.1111\/epi.17656","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T05:48:09Z","timestamp":1684475289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["A novel <i>KCNC1<\/i> gain\u2010of\u2010function variant causing developmental and epileptic encephalopathy: \u201cPrecision medicine\u201d approach with fluoxetine"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-5551","authenticated-orcid":false,"given":"Paolo","family":"Ambrosino","sequence":"first","affiliation":[{"name":"Department of Science and Technology University of Sannio  Benevento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1399-8271","authenticated-orcid":false,"given":"Francesca","family":"Ragona","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico C. Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Mosca","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Science University of Molise  Campobasso Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Vannicola","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico C. Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5385-761X","authenticated-orcid":false,"given":"Laura","family":"Canafoglia","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Technology Fondazione IRCCS Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-3328","authenticated-orcid":false,"given":"Roberta","family":"Solazzi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico C. Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Rivolta","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery University of Milano\u2010Bicocca  Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2293-8687","authenticated-orcid":false,"given":"Elena","family":"Freri","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico C. Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0170-6836","authenticated-orcid":false,"given":"Tiziana","family":"Granata","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuroscience Fondazione IRCCS Istituto Neurologico C. Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5889-2342","authenticated-orcid":false,"given":"Giuliana","family":"Messina","sequence":"additional","affiliation":[{"name":"Unit of Genetics of Neurodegenerative and Metabolic Diseases Fondazione IRCCS Istituto Neurologico C. Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-3041","authenticated-orcid":false,"given":"Barbara","family":"Castellotti","sequence":"additional","affiliation":[{"name":"Unit of Genetics of Neurodegenerative and Metabolic Diseases Fondazione IRCCS Istituto Neurologico C. Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3582-665X","authenticated-orcid":false,"given":"Cinzia","family":"Gellera","sequence":"additional","affiliation":[{"name":"Unit of Genetics of Neurodegenerative and Metabolic Diseases Fondazione IRCCS Istituto Neurologico C. Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3601-9374","authenticated-orcid":false,"given":"Maria Virginia","family":"Soldovieri","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Science University of Molise  Campobasso Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4102-1188","authenticated-orcid":false,"given":"Jacopo Cosimo","family":"DiFrancesco","sequence":"additional","affiliation":[{"name":"Department of Neurology Fondazione IRCCS San Gerardo dei Tintori  Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8202-0560","authenticated-orcid":false,"given":"Maurizio","family":"Taglialatela","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00002.2017"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3144"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1684\/epd.2016.0859"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-21-1885"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50799"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.50822"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00257.2021"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.3"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51707"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310501200"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(01)00088-0"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.FP0070759"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29594-w"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.01289"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(00)00116-0"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858418763752"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb11295.x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24929"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2021_502"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.17656","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T22:26:57Z","timestamp":1692224817000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.17656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,2]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1111\/epi.17656"],"URL":"https:\/\/doi.org\/10.1111\/epi.17656","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,2]]},"assertion":[{"value":"2023-01-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}