{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T21:05:06Z","timestamp":1765487106466,"version":"3.44.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004332","name":"Seoul National University Hospital","doi-asserted-by":"publisher","award":["0320200350","0320210170"],"award-info":[{"award-number":["0320200350","0320210170"]}],"id":[{"id":"10.13039\/501100004332","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018688","name":"Korea Disease Control and Prevention Agency","doi-asserted-by":"publisher","award":["2020\u2010ER6904\u201001"],"award-info":[{"award-number":["2020\u2010ER6904\u201001"]}],"id":[{"id":"10.13039\/100018688","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Epilepsy is a suitable target for gene panel sequencing because a considerable portion of epilepsy is now explained by genetic components, especially in syndromic cases. However, previous gene panel studies on epilepsy have mostly focused on pediatric patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled adult epilepsy patients meeting any of the following criteria: family history of epilepsy, seizure onset age\u2009\u2264\u200919\u2009years, neuronal migration disorder, and seizure freedom not achieved by dual anti\u2010seizure medications. We sequenced the exonic regions of 211 epilepsy genes in these patients. To confirm the pathogenicity of a novel <jats:italic>MTOR<\/jats:italic> truncating variant, we electroporated vectors with different <jats:italic>MTOR<\/jats:italic> variants into developing mouse brains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 92 probands and 4 affected relatives were tested, and the proportion of intellectual disability (ID) and\/or developmental disability (DD) was 21.7%. As a result, twelve probands (13.0%) had pathogenic or likely pathogenic variants in the following genes or regions: <jats:italic>DEPDC5<\/jats:italic>, 15q12\u2010q13 duplication (<jats:italic>n<\/jats:italic>\u2009=\u20092), <jats:italic>SLC6A1<\/jats:italic>, <jats:italic>SYNGAP1<\/jats:italic>, <jats:italic>EEF1A2<\/jats:italic>, <jats:italic>LGI1<\/jats:italic>, <jats:italic>MTOR<\/jats:italic>, <jats:italic>KCNQ2<\/jats:italic>, <jats:italic>MEF2C<\/jats:italic>, and <jats:italic>TSC1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u2009=\u20091). We confirmed the functional impact of a novel truncating mutation in the <jats:italic>MTOR<\/jats:italic> gene (c.7570C\u2009&gt;\u2009T, p.Gln2524Ter) that disrupted neuronal migration in a mouse model. The diagnostic yield was higher in patients with ID\/DD or childhood\u2010onset seizures. We also identified additional candidate variants in 20 patients that could be reassessed by further studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Our findings underscore the clinical utility of gene panel sequencing in adult epilepsy patients suspected of having genetic etiology, especially those with ID\/DD or early\u2010onset seizures. Gene panel sequencing could not only lead to genetic diagnosis in a substantial portion of adult epilepsy patients but also inform more precise therapeutic decisions based on their genetic background.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>This study demonstrated the effectiveness of gene panel sequencing in adults with epilepsy, revealing pathogenic or likely pathogenic variants in 13.0% of patients. Higher diagnostic yields were observed in those with neurodevelopmental disorders or childhood\u2010onset seizures. Additionally, we have shown that expanding genetic studies into adult patients would uncover new types of pathogenic variants for epilepsy, contributing to the advancement of precision medicine for individuals with epilepsy. In conclusion, our results highlight the practical value of employing gene panel sequencing in adult epilepsy patients, particularly when genetic etiology is clinically suspected.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.12993","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T03:04:18Z","timestamp":1719803058000},"page":"1538-1549","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Broadening the scope of multigene panel analysis for adult epilepsy patients"],"prefix":"10.1002","volume":"9","author":[{"given":"Seungbok","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Genomic Medicine Seoul National University Hospital  Seoul Korea"},{"name":"Department of Pediatrics Seoul National University College of Medicine, Seoul National University Children's Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi\u2010Kyoung","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University College of Medicine, Seoul National University Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki Hurn","family":"So","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Pohang University of Science and Technology (POSTECH)  Pohang Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riyul","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Pohang University of Science and Technology (POSTECH)  Pohang Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong Woo","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University College of Medicine, Seoul National University Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6299-0228","authenticated-orcid":false,"given":"Se Song","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Seoul National University College of Medicine, Seoul National University Children's Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-7803","authenticated-orcid":false,"given":"Jihoon G.","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Seoul National University Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheehyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Seoul National University Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manjin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Seoul National University Hospital  Seoul Korea"},{"name":"Department of Laboratory Medicine Seoul National University College of Medicine, Seoul National University Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-0302","authenticated-orcid":false,"given":"Kon","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University College of Medicine, Seoul National University Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1908-0699","authenticated-orcid":false,"given":"Sang Kun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurology Seoul National University College of Medicine, Seoul National University Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki Joong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Seoul National University College of Medicine, Seoul National University Children's Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Tae","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Pohang University of Science and Technology (POSTECH)  Pohang Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8509-4135","authenticated-orcid":false,"given":"Byung Chan","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Seoul National University College of Medicine, Seoul National University Children's Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1282-4528","authenticated-orcid":false,"given":"Jangsup","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine Seoul National University Hospital  Seoul Korea"},{"name":"Department of Neurology Seoul National University College of Medicine, Seoul National University Hospital  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16273"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30269-8"},{"key":"e_1_2_12_4_1","first-page":"D845","article-title":"The DisGeNET knowledge platform for disease genomics: 2019 update","volume":"48","author":"Pinero J","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1711801"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu030"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011655"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.944905"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13031"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23822"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00988"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13903"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16427"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306555"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/1550059419876518"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16533"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa029"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz195"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16640"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6421039"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14087"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr129"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/CON.0000000000000707"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.004"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-021-00835-9"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3466"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.05.039"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.03.005"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000650"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14074"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2016.06.019"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.12954"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12348"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12394"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.219"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3982"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2260-18.2019"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3824"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.12993","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T11:47:56Z","timestamp":1755863276000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.12993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/epi4.12993"],"URL":"https:\/\/doi.org\/10.1002\/epi4.12993","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"type":"print","value":"2470-9239"},{"type":"electronic","value":"2470-9239"}],"subject":[],"published":{"date-parts":[[2024,7]]},"assertion":[{"value":"2023-09-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}