{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:38:21Z","timestamp":1793205501404,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the frequency of monogenic variants and pathogenic copy number variants (CNVs) in adults with surgically treated temporal lobe epilepsy (TLE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed exome sequencing (ES), including CNV analysis, in 45 adults with TLE who had previously undergone epilepsy surgery. A diagnostic exome\u2010wide analysis was conducted to identify (likely) pathogenic variants related to epilepsy. In an exploratory approach, we screened a curated list of 45 common epilepsy genes for rare deleterious variants based on AlphaMissense and REVEL in silico predictions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No highly penetrant monogenic variants were identified in this cohort. Pathogenic CNVs were detected in two individuals, corresponding to 4.4% of the cohort: a 16p13.11 deletion in a surgery responder and a 22q11.2 duplication in a surgery nonresponder. Both CNVs are characterized by reduced penetrance and broad phenotypic variability. Moreover, we identified two predicted deleterious missense variants in the epilepsy\u2010associated genes\n                      <jats:italic>KCNT1<\/jats:italic>\n                      and\n                      <jats:italic>SLC2A1<\/jats:italic>\n                      , both of which were detected in surgery nonresponders. In silico analyses, including structural evidence, suggested a potential impact on protein function; however, their clinical significance remains uncertain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Monogenic causes are exceedingly rare in adults with surgically treated TLE, whereas CNVs may contribute to disease susceptibility in a small subset of patients. Our findings are consistent with previous reports indicating a low diagnostic yield of presurgical genetic testing and further support a predominantly polygenic architecture of TLE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>Temporal lobe epilepsy (TLE) is a common type of epilepsy in adults, and some patients undergo surgery when medications fail. It is unclear whether genetic testing can help predict surgical success. In this study, we used comprehensive genetic testing in 45 adult TLE patients who had undergone epilepsy surgery. We did not find single\u2010gene causes of epilepsy. Two patients had structural genetic changes, which increase epilepsy risk but show variable effects. We also identified a few rare variants in epilepsy\u2010related genes, but their clinical relevance remains uncertain. Overall, our results suggest that single\u2010gene causes are rare in adults with TLE. Genetic testing may therefore have a low diagnostic rate in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70350","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:14:52Z","timestamp":1787919292000},"page":"1853-1862","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rare genetic variation in adults with surgically treated temporal lobe epilepsy: An exome sequencing study"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1271-7510","authenticated-orcid":false,"given":"Antonia P.","family":"Pirker","sequence":"first","affiliation":[{"name":"Department of Neurology Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences &amp; Mental Health Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Ernst","sequence":"additional","affiliation":[{"name":"Department of Pathobiology of the Nervous System, Center for Brain Research Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-8823","authenticated-orcid":false,"given":"Matias","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia B.","family":"Bonelli","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences &amp; Mental Health Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Trimmel","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences &amp; Mental Health Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9997-341X","authenticated-orcid":false,"given":"Judith","family":"Jud","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences &amp; Mental Health Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Graf","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1843-7732","authenticated-orcid":false,"given":"Christian","family":"Dorfer","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical University of Vienna  Vienna Austria"},{"name":"Department of Neurosurgery University Hospital St. P\u00f6lten  St. P\u00f6lten Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9249-8082","authenticated-orcid":false,"given":"Karl","family":"R\u00f6ssler","sequence":"additional","affiliation":[{"name":"Comprehensive Center for Clinical Neurosciences &amp; Mental Health Medical University of Vienna  Vienna Austria"},{"name":"Department of Neurosurgery Medical University of Vienna  Vienna 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