{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:58:01Z","timestamp":1789070281047,"version":"build-2803163510"},"reference-count":20,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T00:00:00Z","timestamp":1729900800000},"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"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We studied the distribution of germline and somatic variants in epilepsy surgery patients with (suspected) malformations of cortical development (MCD) who underwent surgery between 2015 and 2020 at University Medical Center Utrecht (the Netherlands) and pooled our data with four previously published cohort studies. Tissue analysis yielded a pathogenic variant in 203 of 663 (31%) combined cases. In 126 of 379 (33%) focal cortical dysplasia (FCD) type II cases and 23 of 37 (62%) hemimegalencephaly cases, a pathogenic variant was identified, mostly involving the mTOR signaling pathway. Pathogenic variants in 10 focal epilepsy genes were found in 48 of 178 (27%) FCDI\/mild MCD\/mMCD with oligodendroglial hyperplasia and epilepsy cases; 36 of these (75%) were <jats:italic>SLC35A2<\/jats:italic> variants. Six of 69 (9%) patients without a histopathological lesion had a pathogenic variant in <jats:italic>SLC35A2<\/jats:italic> (<jats:italic>n<\/jats:italic> =\u20095) or <jats:italic>DEPDC5<\/jats:italic> (<jats:italic>n<\/jats:italic> =\u20091). A germline variant in blood DNA was confirmed in all cases with a pathogenic variant in tissue, with a variant allele frequency (VAF) of ~50%. In seven of 114 patients (6%) with a somatic variant in tissue, mosaicism in blood was detected. More than half of pathogenic somatic variants had a VAF &lt;\u20095%. Further analysis of the correlation between genetic variants and surgical outcomes will improve patient counseling and may guide postoperative treatment decisions.<\/jats:p>","DOI":"10.1111\/epi.18148","type":"journal-article","created":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T12:39:20Z","timestamp":1729946360000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Somatic variant analysis of resected brain tissue in epilepsy surgery patients"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0592-1098","authenticated-orcid":false,"given":"Maurits W. C. B.","family":"Sanders","sequence":"first","affiliation":[{"name":"Department of Child Neurology University Medical Center Utrecht Brain Center  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7749-182X","authenticated-orcid":false,"given":"Bobby P. C.","family":"Koeleman","sequence":"additional","affiliation":[{"name":"Department of Genetics, Center for Molecular Medicine University Medical Center  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5793-9623","authenticated-orcid":false,"given":"Eva H.","family":"Brilstra","sequence":"additional","affiliation":[{"name":"Department of Genetics, Center for Molecular Medicine University Medical Center  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-5668","authenticated-orcid":false,"given":"Floor E.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Child Neurology University Medical Center Utrecht Brain Center  Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4851-2796","authenticated-orcid":false,"given":"Sara","family":"Baldassari","sequence":"additional","affiliation":[{"name":"H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re, Institut du Cerveau\u2013Paris Brain Institute Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8454-7374","authenticated-orcid":false,"given":"Mathilde","family":"Chipaux","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurosurgery Rothschild Foundation Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5567-8076","authenticated-orcid":false,"given":"Nam Suk","family":"Sim","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3008-8432","authenticated-orcid":false,"given":"Ara","family":"Ko","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, Pediatric Epilepsy Clinics Severance Children's Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3659-8847","authenticated-orcid":false,"given":"Hoon\u2010Chul","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Pediatrics, Pediatric Epilepsy Clinics Severance Children's Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8676-0788","authenticated-orcid":false,"given":"Ingmar","family":"Bl\u00fcmcke","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Hospital Erlangen  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5173-9636","authenticated-orcid":false,"given":"Dennis","family":"Lal","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute, Lerner Research Institute Cleveland Clinic  Cleveland Ohio United\u00a0States"},{"name":"Cologne Center for Genomics, Faculty of Medicine and University Hospital Cologne University of Cologne  Cologne Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6430-4693","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Baulac","sequence":"additional","affiliation":[{"name":"H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re, Institut du Cerveau\u2013Paris Brain Institute Sorbonne Universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3542-3770","authenticated-orcid":false,"given":"Eleonora","family":"Aronica","sequence":"additional","affiliation":[{"name":"Department of (Neuro)Pathology, Amsterdam Neuroscience Amsterdam University Medical Center  Amsterdam the Netherlands"},{"name":"Stichting Epilepsie Instellingen Nederland  Heemstede the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3631-0003","authenticated-orcid":false,"given":"Kees P. 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