{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:04:18Z","timestamp":1747184658979,"version":"3.40.5"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T00:00:00Z","timestamp":1617753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007929","name":"Institute for Translational Medicine and Therapeutics","doi-asserted-by":"publisher","award":["UL1TR0018"],"award-info":[{"award-number":["UL1TR0018"]}],"id":[{"id":"10.13039\/100007929","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01DA036751","R01NS4930601","R21NS095756","T32MH014654"],"award-info":[{"award-number":["K01DA036751","R01NS4930601","R21NS095756","T32MH014654"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009670","name":"National Alliance for Research on Schizophrenia and Depression","doi-asserted-by":"publisher","award":["26634"],"award-info":[{"award-number":["26634"]}],"id":[{"id":"10.13039\/100009670","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine if long interspersed element\u20101 (L1) retrotransposons convey risk for idiopathic temporal lobe epilepsy (TLE).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Surgically resected temporal cortex from individuals with TLE (<jats:italic>N<\/jats:italic>\u00a0=\u00a033) and postmortem temporal cortex from individuals with no known neurological disease (<jats:italic>N<\/jats:italic>\u00a0=\u00a033) were analyzed for L1 content by Restriction Enzyme Based Enriched L1Hs sequencing (REBELseq). Expression of three <jats:italic>KCNIP4<\/jats:italic> splice variants was assessed by droplet digital PCR (ddPCR). Protein ANalysis THrough Evolutionary Relationships (PANTHER) was used to determine ontologies and pathways for lists of genes harboring L1 insertions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified novel L1 insertions specific to individuals with TLE, and others specific to controls. Although there were no statistically significant differences between cases and controls in the numbers of known and novel L1 insertions, PANTHER analyses of intragenic L1 insertions showed statistically significant enrichments for epilepsy\u2010relevant gene ontologies in both cases and controls. Gene ontologies \u201cneuron projection development\u201d and \u201ccalcium ion transmembrane transport\u201d were among those found only in individuals with TLE. We confirmed novel L1 insertions in several genes associated with seizures\/epilepsy, including a de novo somatic L1 retrotransposition in <jats:italic>KCNIP4<\/jats:italic> that occurred after neural crest formation in one patient. However, ddPCR results suggest this de novo L1 did not alter <jats:italic>KCNIP4<\/jats:italic> mRNA expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Given current data from this small cohort, we conclude that L1 elements, either rare heritable germline insertions or de novo somatic retrotranspositions, may contribute only minimally to overall genetic risk for idiopathic TLE. We suggest that further studies in additional patients and additional brain regions are warranted.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16897","type":"journal-article","created":{"date-parts":[[2021,4,7]],"date-time":"2021-04-07T12:09:23Z","timestamp":1617797363000},"page":"1329-1342","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Investigation of long interspersed element\u20101 retrotransposons as potential risk factors for idiopathic temporal lobe epilepsy"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3859-2470","authenticated-orcid":false,"given":"Glenn A.","family":"Doyle","sequence":"first","affiliation":[{"name":"Department of Psychiatry Center for Neurobiology and Behavior University of Pennsylvania Perelman School of Medicine Philadelphia PA 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S.","family":"Ojeah","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Center for Neurobiology and Behavior University of Pennsylvania Perelman School of Medicine Philadelphia PA USA"},{"name":"Lincoln University of School of Natural Sciences and Mathematics Lincoln University Lincoln PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriella","family":"Arauco\u2010Shapiro","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Center for Neurobiology and Behavior University of Pennsylvania Perelman School of Medicine Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel N.","family":"Levinson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Center for Neurobiology and Behavior University of Pennsylvania Perelman School of Medicine Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lokesh 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