{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:17:10Z","timestamp":1790806630630,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T00:00:00Z","timestamp":1710547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["16\/RC\/3948"],"award-info":[{"award-number":["16\/RC\/3948"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The contribution of somatic variants to epilepsy has recently been demonstrated, particularly in the etiology of malformations of cortical development. The aim of this study was to determine the diagnostic yield of somatic variants in genes that have been previously associated with a somatic or germline epilepsy model, ascertained from resected brain tissue from patients with multidrug\u2010resistant focal epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty\u2010two patients were recruited across three categories: (1) malformations of cortical development, (2) mesial temporal lobe epilepsy with hippocampal sclerosis, and (3) nonlesional focal epilepsy. Participants were subdivided based on histopathology of the resected brain. Paired blood\u2010 and brain\u2010derived DNA samples were sequenced using high\u2010coverage targeted next generation sequencing to high depth (585\u00d7 and 1360\u00d7, respectively). Variants were identified using Genome Analysis ToolKit (GATK4) MuTect\u20102 and confirmed using high\u2010coverage Amplicon\u2010EZ sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sequence data on 41 patients passed quality control. Four somatic variants were validated following amplicon sequencing: within <jats:italic>CBL<\/jats:italic>, <jats:italic>ALG13<\/jats:italic>, <jats:italic>MTOR<\/jats:italic>, and <jats:italic>FLNA<\/jats:italic>. The diagnostic yield across 41 patients was 10%, 9% in mesial temporal lobe epilepsy with hippocampal sclerosis and 20% in malformations of cortical development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study provides novel insights into the etiology of mesial temporal lobe epilepsy with hippocampal sclerosis, highlighting a potential pathogenic role of somatic variants in <jats:italic>CBL<\/jats:italic> and <jats:italic>ALG13<\/jats:italic>. We also report candidate diagnostic somatic variants in <jats:italic>FLNA<\/jats:italic> in focal cortical dysplasia, while providing further insight into the importance of <jats:italic>MTOR<\/jats:italic> and related genes in focal cortical dysplasia. This work demonstrates the potential molecular diagnostic value of variants in both germline and somatic epilepsy genes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17943","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T14:15:50Z","timestamp":1710598550000},"page":"1451-1461","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Somatic variants as a cause of drug\u2010resistant epilepsy including mesial temporal lobe epilepsy with hippocampal sclerosis"],"prefix":"10.1111","volume":"65","author":[{"given":"Robert J.","family":"Carton","sequence":"first","affiliation":[{"name":"FutureNeuro Science Foundation Ireland Research Centre Royal College of Surgeons in Ireland  Dublin Ireland"},{"name":"School of Pharmacy and Biomolecular Sciences Royal College of Surgeons in Ireland  Dublin 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