{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:11:54Z","timestamp":1790820714360,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1091593"],"award-info":[{"award-number":["1091593"]}],"id":[{"id":"10.13039\/501100000925","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":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To analyze clinical phenotypes associated with <jats:italic>KCNC1<\/jats:italic> variants other than the Progressive Myoclonus Epilepsy\u2010causing variant p.Arg320His, determine the electrophysiological functional impact of identified variants and explore genotype\u2010phenotype\u2010physiological correlations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ten cases with putative pathogenic variants in <jats:italic>KCNC1<\/jats:italic> were studied. Variants had been identified via whole\u2010exome sequencing or gene panel testing. Clinical phenotypic data were analyzed. To determine functional impact of variants detected in the K<jats:sub>v<\/jats:sub>3.1 channel encoded by <jats:italic>KCNC1<\/jats:italic>, <jats:italic>Xenopus laevis<\/jats:italic> oocyte expression system and automated two\u2010electrode voltage clamping were used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six unrelated patients had a Developmental and Epileptic Encephalopathy and a recurrent <jats:italic>de novo<\/jats:italic> variant p.Ala421Val (c.1262C\u00a0&gt;\u00a0T). Functional analysis of p.Ala421Val revealed loss of function through a significant reduction in whole\u2010cell current, but no dominant\u2010negative effect. Three patients had a contrasting phenotype of Developmental Encephalopathy without seizures and different <jats:italic>KCNC1<\/jats:italic> variants, all of which caused loss of function with reduced whole\u2010cell currents. Evaluation of the variant p.Ala513Val (c.1538C\u00a0&gt;\u00a0T) in the tenth case, suggested it was a variant of uncertain significance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These are the first reported cases of Developmental and Epileptic Encephalopathy due to <jats:italic>KCNC1<\/jats:italic> mutation. The spectrum of phenotypes associated with <jats:italic>KCNC1<\/jats:italic> is now broadened to include not only a Progressive Myoclonus Epilepsy, but an infantile onset Developmental and Epileptic Encephalopathy, as well as Developmental Encephalopathy without seizures. Loss of function is a key feature, but definitive electrophysiological separation of these phenotypes has not yet emerged.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50822","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T07:53:18Z","timestamp":1561967598000},"page":"1263-1272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Encephalopathies with <i>KCNC1<\/i> variants: genotype\u2010phenotype\u2010functional correlations"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2175-5977","authenticated-orcid":false,"given":"Jillian M.","family":"Cameron","sequence":"first","affiliation":[{"name":"Epilepsy Research Centre, Department of Medicine University of Melbourne, Austin Health Heidelberg Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snezana","family":"Maljevic","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umesh","family":"Nair","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye Htet","family":"Aung","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Cogn\u00e9","sequence":"additional","affiliation":[{"name":"L'institut du thorax INSERM, CNRS, UNIV Nantes Nantes France"},{"name":"Service de g\u00e9n\u00e9tique medicale Centre Hospitalier, Universit\u00e9 de Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"B\u00e9zieau","sequence":"additional","affiliation":[{"name":"L'institut du thorax INSERM, CNRS, UNIV Nantes Nantes France"},{"name":"Service de g\u00e9n\u00e9tique medicale Centre Hospitalier, Universit\u00e9 de Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Blair","sequence":"additional","affiliation":[{"name":"Oxford Centre for Genomic Medicine, ACE Building Nuffield Orthopaedic Centre Windmill Road Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[{"name":"L'institut du thorax INSERM, CNRS, UNIV Nantes Nantes France"},{"name":"Service de g\u00e9n\u00e9tique medicale Centre Hospitalier, Universit\u00e9 de Nantes Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Zweier","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Reis","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg (FAU) Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Kay","family":"Koenig","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Division of Child &amp; Adolescent Neurology The University of Texas McGovern Medical School Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Maarup","sequence":"additional","affiliation":[{"name":"Southern California Permanente Medical Group Pasadena California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Sarco","sequence":"additional","affiliation":[{"name":"Southern California Permanente Medical Group Pasadena California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Afenjar","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence des malformations et maladies cong\u00e9nitales du cervelet, D\u00e9partement de g\u00e9n\u00e9tique m\u00e9dicale Sorbonne Universit\u00e9, GRC ConCer\u2010LD, AP\u2010HP, H\u00f4pital Armand Trousseau F\u201075012 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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