{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:20:10Z","timestamp":1784593210975,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"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"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Fibroblast growth factor 12 (\n                      <jats:italic>FGF12<\/jats:italic>\n                      ), a member of the fibroblast homologous factor family, plays a key role in the modulation of voltage\u2010gated sodium (Nav) channels. Pathogenic variants in the\n                      <jats:italic>FGF12<\/jats:italic>\n                      gene leading to a gain\u2010of\u2010function mechanism and partial duplication encompassing the\n                      <jats:italic>FGF12<\/jats:italic>\n                      gene leading to a loss\u2010of\u2010function mechanism are associated with developmental and epileptic encephalopathy (DEE), characterized by developmental delay, intellectual disability, ataxia, and drug\u2010resistant epilepsy. We report two patients with DEE harboring de novo recurrent intragenic duplications of\n                      <jats:italic>FGF12<\/jats:italic>\n                      identified by long\u2010read sequencing (LRS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We applied LRS to the DNA and cDNA of patients with\n                      <jats:italic>FGF12<\/jats:italic>\n                      duplication to fully characterize the DNA's structural organization and its transcriptional consequences. Additionally, we reanalyzed electroencephalographic (EEG) data from patients at different timepoints to identify phenotypical specificities and refine the electroclinical spectrum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>These duplications, spanning approximately 536\u2009kbp, were mediated by nonallelic homologous recombination between L1PA2 elements (LINE\u20101 Primate\u2010specific subfamily A, number 2). cDNA analysis revealed aberrant transcripts, one predicted to encode an elongated FGF12 protein and another leading to premature termination. Both patients shared overlapping clinical features, including postepilepsy onset regression, global developmental delay, and ataxia. EEG studies revealed a marked early encephalopathic pattern with disorganized and high\u2010voltage slow background activity with multifocal spikes at onset evolving later into subcontinuous generalized spike and wave activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Our findings are consistent with previous reports linking structural variants to functional disruption, suggesting impaired Nav channel activity due to a shift in inactivation to hyperpolarized potential, leading to a loss\u2010of\u2010function effect. These findings underscore the utility of LRS for DNA and cDNA analysis in resolving structural variants and expanding the electroclinical spectrum of patients with\n                      <jats:italic>FGF12<\/jats:italic>\n                      duplications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18609","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T14:00:15Z","timestamp":1755784815000},"page":"5014-5032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Long\u2010read sequencing of recurrent\n                    <i>FGF12<\/i>\n                    duplications in epilepsy: Insights into structural mechanisms and aberrant isoforms"],"prefix":"10.1111","volume":"66","author":[{"given":"Jade","family":"Fauqueux","sequence":"first","affiliation":[{"name":"Univ. Lille, Unit\u00e9 de Recherche ULR7364 RADEME \u2010 Maladies RAres du D\u00c9veloppement F\u00e9d\u00e9ration Hospitalo\u2010Universitaire FHU\u2010G4 G\u00e9nomique  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Chaton","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Lille Service de Neurophysiologie Clinique  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Cleuziou","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Lille Clinique de P\u00e9diatrie, Service de Neurop\u00e9diatrie  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Sophie","family":"Diependa\u00eble","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Caen Service de Neurologie Unit\u00e9 Explorations Fonctionnelles Neurologiques  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Bach","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Caen Service de P\u00e9diatrie  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Gruchy","sequence":"additional","affiliation":[{"name":"Univ. Caen Normandie, Unit\u00e9 de Recherche UR7450 BioTARGen, F\u00e9d\u00e9ration Hospitalo\u2010Universitaire FHU\u2010G4 G\u00e9nomique Centre Hospitalier Universitaire de Caen, Service de G\u00e9n\u00e9tique  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Gerard","sequence":"additional","affiliation":[{"name":"Univ. Caen Normandie, Unit\u00e9 de Recherche UR7450 BioTARGen, F\u00e9d\u00e9ration Hospitalo\u2010Universitaire FHU\u2010G4 G\u00e9nomique Centre Hospitalier Universitaire de Caen, Service de G\u00e9n\u00e9tique  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Pascal","family":"Meneboo","sequence":"additional","affiliation":[{"name":"Univ. Lille, Centre National de la Recherche Scientifique CNRS, Inserm, Centre Hospitalier Universitaire de Lille Institut Pasteur de Lille, Plateformes Lilloises en Biologie &amp; Sant\u00e9  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Villenet","sequence":"additional","affiliation":[{"name":"Univ. Lille, Centre National de la Recherche Scientifique CNRS, Inserm, Centre Hospitalier Universitaire de Lille Institut Pasteur de Lille, Plateformes Lilloises en Biologie &amp; Sant\u00e9  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Figeac","sequence":"additional","affiliation":[{"name":"Univ. Lille, Centre National de la Recherche Scientifique CNRS, Inserm, Centre Hospitalier Universitaire de Lille Institut Pasteur de Lille, Plateformes Lilloises en Biologie &amp; Sant\u00e9  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Ait\u2010Yahya","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Lille, Cellule de Bioinformatique Plateau Commun de S\u00e9quen\u00e7age  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Thuillier","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Lille Institut de G\u00e9n\u00e9tique M\u00e9dicale  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Boudry","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Lille Institut de G\u00e9n\u00e9tique M\u00e9dicale  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adeline","family":"Trauffler","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Lille Clinique de P\u00e9diatrie, Service de Neurop\u00e9diatrie  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Nguyen\u2010The\u2010Tich","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Lille Clinique de P\u00e9diatrie, Service de Neurop\u00e9diatrie  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Boussion","sequence":"additional","affiliation":[{"name":"Univ. Lille, Unit\u00e9 de Recherche ULR7364 RADEME \u2010 Maladies RAres du D\u00c9veloppement F\u00e9d\u00e9ration Hospitalo\u2010Universitaire FHU\u2010G4 G\u00e9nomique  Lille France"},{"name":"Centre Hospitalier Universitaire de Lille Clinique de G\u00e9n\u00e9tique  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roseline","family":"Caumes","sequence":"additional","affiliation":[{"name":"Univ. Lille, Unit\u00e9 de Recherche ULR7364 RADEME \u2010 Maladies RAres du D\u00c9veloppement F\u00e9d\u00e9ration Hospitalo\u2010Universitaire FHU\u2010G4 G\u00e9nomique  Lille France"},{"name":"Centre Hospitalier Universitaire de Lille Clinique de G\u00e9n\u00e9tique  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal","family":"Ghoumid","sequence":"additional","affiliation":[{"name":"Univ. 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