{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T22:01:38Z","timestamp":1792879298644,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,6]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n \n Dravet syndrome (DS) is a developmental and epileptic encephalopathy. Diagnosis is clinical, but ~90% of patients have pathogenic variants in\n SCN1A<\/jats:italic>\n .\n ATP6V0C<\/jats:italic>\n has recently been proposed as a novel candidate gene for epilepsy, with or without developmental delay. Here we describe two adult patients with a clinical diagnosis of DS associated with\n ATP6V0C<\/jats:italic>\n variants.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Patients with developmental and epileptic encephalopathies were evaluated by physicians who are experts in DS, and their clinical diagnosis was correlated with genetic findings. A subgroup of those patients with DS but without known genetic causes were evaluated through gene panels, whole exome sequencing, and chromosome microarray. Phenotype was determined by pediatric and adult chart reviews, interviews, and physical examinations.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 753 patients with DS, two unrelated individuals with classic features of DS during childhood and adulthood were identified with heterozygous de novo missense variants in\n ATP6V0C<\/jats:italic>\n (c.319G\u2009>\u2009C, p.(Gly107Arg) and c.284C\u2009>\u2009T, p.(Ala95Val), respectively). Both variants were absent in normal populations and computational prediction algorithms suggested deleterious effects on protein structure and\/or function. No disease\u2010causing variants in other genes previously associated with DS were found.\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n \n Here we describe two adult patients with Dravet\u2010like syndrome and pathogenic\/likely pathogenic variants in\n ATP6V0C<\/jats:italic>\n . We propose that abnormal\n ATP6V0C<\/jats:italic>\n function can, at the severe end of the clinical spectrum, be associated with Dravet\u2010like phenotype. This is relevant, as these patients would not qualify for disease\u2010modifying antisense nucleotide or gene therapies targeting\n SCN1A<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/epi.18346","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T12:14:16Z","timestamp":1741954456000},"page":"2046-2052","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Variants in\n ATP6V0C<\/i>\n are associated with Dravet\u2010like developmental and epileptic encephalopathy"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-4932","authenticated-orcid":false,"given":"Marlene","family":"Rong","sequence":"first","affiliation":[{"name":"Adult Genetic Epilepsy (AGE) Program, Krembil Brain Institute, Toronto Western Hospital University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1303-9273","authenticated-orcid":false,"given":"Paula T.","family":"Marques","sequence":"additional","affiliation":[{"name":"Adult Genetic Epilepsy (AGE) Program, Krembil Brain Institute, Toronto Western Hospital University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3984-5276","authenticated-orcid":false,"given":"Quratulain Zulfiqar","family":"Ali","sequence":"additional","affiliation":[{"name":"Adult Genetic Epilepsy (AGE) Program, Krembil Brain Institute, Toronto Western Hospital University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6441-6767","authenticated-orcid":false,"given":"Ricardo","family":"Morcos","sequence":"additional","affiliation":[{"name":"Epilepsy and Neurogenetics Unit, Vithas Madrid University Hospitals Universidad Europea de Madrid Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9576-9001","authenticated-orcid":false,"given":"Ilakkiah","family":"Chandran","sequence":"additional","affiliation":[{"name":"Adult Genetic Epilepsy (AGE) Program, Krembil Brain Institute, Toronto Western Hospital University of Toronto Toronto Ontario Canada"},{"name":"Institute of Medical Science University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1050-2533","authenticated-orcid":false,"given":"Farah","family":"Qaiser","sequence":"additional","affiliation":[{"name":"Adult Genetic Epilepsy (AGE) Program, Krembil Brain Institute, Toronto Western Hospital University of Toronto Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9664-1448","authenticated-orcid":false,"given":"Rikke S.","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Epilepsy Genetics and Personalized Medicine Danish Epilepsy Centre Dianalund Denmark"},{"name":"Member of the European Reference Center EpiCARE Dianalund Denmark"},{"name":"Department of Regional Health Research, Faculty of Health Sciences University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4986-8006","authenticated-orcid":false,"given":"Allan","family":"Bayat","sequence":"additional","affiliation":[{"name":"Department of Drug Design and Pharmacology University of Copenhagen Copenhagen Denmark"},{"name":"Department for Genetics and Personalized Medicine Danish Epilepsy Centre Dianalund Denmark"},{"name":"Institute for Regional Health Services University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5309-2514","authenticated-orcid":false,"given":"Guido","family":"Rubboli","sequence":"additional","affiliation":[{"name":"Danish Epilepsy Center, Member of the European Reference Center EpiCARE Dianalund Denmark"},{"name":"University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7138-6022","authenticated-orcid":false,"given":"Elena","family":"Gardella","sequence":"additional","affiliation":[{"name":"Department of Epilepsy Genetics and Personalized Medicine Danish Epilepsy Centre Dianalund Denmark"},{"name":"Member of the European Reference Center EpiCARE Dianalund Denmark"},{"name":"Department of Regional Health Research, Faculty of Health Sciences University of Southern Denmark Odense Denmark"},{"name":"Department of Clinical Neurophysiology, Danish Epilepsy Centre Dianalund Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8662-6685","authenticated-orcid":false,"given":"Miriam S.","family":"Reuter","sequence":"additional","affiliation":[{"name":"The Centre for Applied Genomics The Hospital for Sick Children Toronto Ontario Canada"},{"name":"Program in Genetics and Genome Biology The Hospital for Sick Children Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7285-1195","authenticated-orcid":false,"given":"Tristan T.","family":"Sands","sequence":"additional","affiliation":[{"name":"Department of Neurology Columbia University Vagelos College of Physicians and Surgeons New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2311-2174","authenticated-orcid":false,"given":"Ingrid E.","family":"Scheffer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Epilepsy Research Centre Austin Health, University of Melbourne Heidelberg Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5260-7187","authenticated-orcid":false,"given":"Amy","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Medicine, Epilepsy Research Centre Austin Health, University of Melbourne Heidelberg Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7350-5136","authenticated-orcid":false,"given":"Annapurna","family":"Poduri","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Boston Massachusetts USA"},{"name":"Department of Neurology Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3015-8282","authenticated-orcid":false,"given":"Elaine","family":"Wirrell","sequence":"additional","affiliation":[{"name":"Divisions of Child and Adolescent Neurology and Epilepsy, Department of Neurology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5877-4074","authenticated-orcid":false,"given":"Rima","family":"Nabbout","sequence":"additional","affiliation":[{"name":"APHP, Necker Enfants Malades Hospital, Member of the European Reference Center EpiCARE, Institut Imagine INSERM 1163 Universit\u00e9 Paris Cit\u00e9 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2081-8988","authenticated-orcid":false,"given":"Joseph","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco San Francisco California United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5008-0809","authenticated-orcid":false,"given":"Kette","family":"Valente","sequence":"additional","affiliation":[{"name":"Clinic Hospital Faculty of Medicine University of S\u00e3o Paulo (USP) S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3874-9749","authenticated-orcid":false,"given":"St\u00e9phane","family":"Auvin","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 INSERM NeuroDiderot Paris France"},{"name":"APHP, Robert Debr\u00e9 University Hospital, Pediatric Neurology Department CRMR Epilepsies Rares, EpiCare Member Paris France"},{"name":"Institut Universitaire de France (IUF) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1967-0827","authenticated-orcid":false,"given":"Kelly G.","family":"Knupp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neurology, School of Medicine University of Colorado Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7728-6903","authenticated-orcid":false,"given":"Andreas","family":"Brunklaus","sequence":"additional","affiliation":[{"name":"School of Health and Wellbeing University of Glasgow Glasgow UK"},{"name":"The Paediatric Neurosciences Research Group Royal Hospital for Children Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4889-3365","authenticated-orcid":false,"given":"\u00c1ngel","family":"Aledo\u2010Serrano","sequence":"additional","affiliation":[{"name":"Epilepsy and Neurogenetics Unit, Vithas Madrid University Hospitals Universidad Europea de Madrid Madrid 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