{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T20:37:43Z","timestamp":1782765463895,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T00:00:00Z","timestamp":1604361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R00HD082337"],"award-info":[{"award-number":["R00HD082337"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K01NS116119"],"award-info":[{"award-number":["K01NS116119"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    ACTL6B is a component of the neuronal BRG1\/brm\u2010associated factor (nBAF) complex, which is required for chromatin remodeling in postmitotic neurons. We recently reported biallelic pathogenic variants in\n                    <jats:italic>ACTL6B<\/jats:italic>\n                    in patients diagnosed with early infantile epileptic encephalopathy, subtype 76 (EIEE\u201076), presenting with severe, global developmental delay, epileptic encephalopathy, cerebral atrophy, and abnormal central nervous system myelination. However, the pathophysiological mechanisms underlying their phenotype is unknown. Here, we investigate the molecular pathogenesis of ACTL6B p.(Val421_Cys425del) using\n                    <jats:italic>in silico<\/jats:italic>\n                    3D protein modeling predictions and patient\u2010specific induced pluripotent stem cell\u2010derived neurons. We found neurons derived from EIEE\u201076 patients showed impaired accumulation of ACTL6B compared to unaffected relatives, caused by reduced protein stability. Furthermore, EIEE\u201076 patient\u2010derived neurons had dysregulated nBAF target gene expression, including genes important for neuronal development and disease. Multielectrode array system analysis unveiled elevated electrophysiological activity of EIEE\u201076 patients\u2010derived neurons, consistent with the patient phenotype. Taken together, our findings validate a new model for EIEE\u201076 and reveal how reduced ACTL6B expression affects neuronal function.\n                  <\/jats:p>","DOI":"10.1002\/jnr.24747","type":"journal-article","created":{"date-parts":[[2020,11,3]],"date-time":"2020-11-03T11:45:11Z","timestamp":1604403911000},"page":"110-123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["An epilepsy\u2010associated ACTL6B variant captures neuronal hyperexcitability in a human induced pluripotent stem cell model"],"prefix":"10.1002","volume":"99","author":[{"given":"Lucie Y.","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Genetics and Genome Sciences Case Western Reserve University Cleveland OH USA"},{"name":"Medical Scientist Training Program Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8140-8400","authenticated-orcid":false,"given":"Giuliana C.","family":"Coatti","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8079-655X","authenticated-orcid":false,"given":"Jingyi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evren","family":"Gumus","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Faculty of Medicine Mugla Sitki Kocman University Mugla Turkey"},{"name":"Department of Medical Genetics Faculty of Medicine University of Harran Sanliurfa Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1164-697X","authenticated-orcid":false,"given":"Ashleigh E.","family":"Schaffer","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences Case Western Reserve University Cleveland OH USA"},{"name":"Center for RNA Science and Therapeutics Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-9790","authenticated-orcid":false,"given":"Helen C.","family":"Miranda","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genome Sciences Case Western Reserve University Cleveland OH USA"},{"name":"Department of Neurosciences Case Western Reserve University Cleveland OH USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,11,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.03.022"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19067"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.32451"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-019-01972-3"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013-9580.2005.66104.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708667105"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00590"},{"issue":"5","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1271\/bbb.63.917","article-title":"Two isoforms of a human actin\u2010related protein show nuclear localization and mutually selective expression between brain 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