{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:44:45Z","timestamp":1790840685424,"version":"4.1.0"},"reference-count":11,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"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 Open"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Familial epilepsy with auditory features (FEAF), previously known as autosomal\u2010dominant lateral temporal lobe epilepsy (ADLTE) is a genetically heterogeneous syndrome, clinically characterized by focal seizures with prominent auditory symptoms. It is inherited with autosomal\u2010dominant pattern with reduced penetrance (about 70%). Sporadic epilepsy with auditory features cases are more frequent and clinically indistinguishable from familial cases. One causal gene, <jats:italic>MICAL\u20101<\/jats:italic>, encodes MICAL\u20101, an intracellular multi\u2010domain enzyme that is an important regulator of filamentous actin (F\u2010actin) structures. Pathogenic variants in <jats:italic>MICAL\u20101<\/jats:italic> account for approximately 7% of FEAF families. Here, we describe a de novo <jats:italic>MICAL\u20101<\/jats:italic> pathogenic variant, p.Arg915Cys, in a sporadic case, an affected 21\u2010year\u2010old Italian man with no family history of epilepsy. Genetic testing was performed in the patient and his parents, using a next\u2010generation sequencing panel. In cell\u2010based assay, this variant significantly increased MICAL\u20101 oxidoreductase activity, which likely resulted in dysregulation of F\u2010actin organization. This finding provides further support for a gain\u2010of\u2010function effect underlying <jats:italic>MICAL\u20101<\/jats:italic>\u2010mediated epilepsy pathogenesis, as previously seen with other pathogenic variants. Furthermore, the case study provides evidence that de novo <jats:italic>MICAL\u20101<\/jats:italic> pathogenic variants can occur in sporadic cases with epilepsy with auditory feature (EAF).<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>In this study, we report a new MICAL\u20101 pathogenic variant in a patient without family history for epilepsy, not inherited from his parents. MICAL\u20101 is a protein with enzymatic activity that reorganizes the structure of the cell. We proved the pathological effect of this variant by testing its enzymatic activity and found an increase of this activity. This result suggests that non\u2010familial cases should be tested to find novel pathogenic variants in this gene.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12937","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T04:40:01Z","timestamp":1713933601000},"page":"1083-1087","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A de novo pathogenic variant in <i><scp>MICAL<\/scp>\u20101<\/i> causes epilepsy with auditory features"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9448-9059","authenticated-orcid":false,"given":"Paolo","family":"Bonanni","sequence":"first","affiliation":[{"name":"Epilepsy and Clinical Neurophysiology Unit IRCCS E. Medea, Scientific Institute  Conegliano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Giorda","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory IRCCS E. Medea, Scientific Institute  Bosisio Parini Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9655-7940","authenticated-orcid":false,"given":"Roberto","family":"Michelucci","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Bellaria Hospital IRCCS Istituto Delle Scienze Neurologiche di Bologna, Epilepsy Center  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0634-2218","authenticated-orcid":false,"given":"Carlo","family":"Nobile","sequence":"additional","affiliation":[{"name":"Section of Padua Neuroscience Institute, National Research Council of Italy  Padova Italy"},{"name":"Department of Biomedical Sciences University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8875-3151","authenticated-orcid":false,"given":"Emanuela","family":"Dazzo","sequence":"additional","affiliation":[{"name":"Section of Padua Neuroscience Institute, National Research Council of Italy  Padova Italy"},{"name":"Department of Biomedical Sciences University of Padua  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17240"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0595-56"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2003.20003.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000120098.39231.6E"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.04.020"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25167"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5646-07.2008"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01389-10"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(99)80018-0"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)00799-2"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr901099e"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12937","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T12:08:04Z","timestamp":1717416484000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,23]]},"references-count":11,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/epi4.12937"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12937","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,23]]},"assertion":[{"value":"2024-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}