{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:49:26Z","timestamp":1791816566231,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"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"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Focal cortical dysplasia (FCD) is a common cause of drug\u2010resistant epilepsy in children and adults and exhibits substantial clinical and histopathological heterogeneity. However, morphological classification alone does not fully explain variability in epileptogenicity, disease severity, or treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We aimed to define molecular mechanisms underlying FCD heterogeneity using integrated transcriptomic and regulatory analyses. RNA and small RNA sequencing (RNA\u2010seq) were conducted on cortical tissue resected during epilepsy surgery from 66 patients with histopathologically confirmed FCD subtypes IA (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200917), IIA (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200925), and IIB (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200924), along with 15 postmortem cortical control samples. Differential expression and weighted gene coexpression network analysis were used to identify coordinated transcriptional programs, and microRNA (miRNA) profiling was integrated to assess posttranscriptional regulatory mechanisms. Integrative multivariate analyses (DIABLO and sparse partial least squares discriminant analysis) were used to evaluate subtype discrimination, and findings were validated using an independent RNA\u2010seq dataset.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>FCD subtypes showed distinct but partially overlapping molecular profiles. FCD IA showed a comparatively subtle transcriptional profile, dominated by reduced expression of genes involved in cortical development, neuronal signaling, ion regulation, and metabolic stress. FCD IIA displayed a modest yet coherent molecular signature involving developmental and neuronal disruption, together with metabolic stress and autophagy. FCD IIB exhibited the most extensive transcriptional remodeling, including activation of antigen presentation pathways, complement activation, cytoskeleton reorganization, synaptic alterations, and extracellular matrix organization. Differential miRNA profiling identified shared miRNAs, including miR\u2010320 family, miR\u201027a\u20105p, miR\u2010142\u20105p, and miR\u201021\u20105p, alongside subtype\u2010specific regulatory patterns. Integration of messenger RNA and miRNA data revealed concordant alterations, indicating that miRNA dysregulation may contribute to stabilization of subtype\u2010specific transcriptional states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These findings demonstrate that FCD is characterized by coordinated transcriptional and posttranscriptional network alterations that extend beyond morphological classification and may contribute to variability in epileptogenicity across subtypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70532","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:33:43Z","timestamp":1791815623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic analysis reveals distinct expression patterns in focal cortical dysplasia"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8475-4289","authenticated-orcid":false,"given":"Shivani","family":"Sonawane","sequence":"first","affiliation":[{"name":"Behavioral and Social Neuroscience Research Group Central European Institute of Technology, Masaryk University  Brno Czech Republic"},{"name":"First Department of Neurology, full member of European Reference Network EpiCARE, Faculty of Medicine, Brno Epilepsy Center St. Anne's University Hospital, Masaryk University  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1024-7408","authenticated-orcid":false,"given":"Michal","family":"Hendrych","sequence":"additional","affiliation":[{"name":"First Department of Pathology, Faculty of Medicine Masaryk University and St. Anne's University Hospital Brno  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5661-6072","authenticated-orcid":false,"given":"Michaela","family":"Ru\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine Central European Institute of Technology, Masaryk University  Brno Czech Republic"},{"name":"Department of Biology, Faculty of Medicine Masaryk University  Brno Czech Republic"},{"name":"Department of Pathology University Hospital Brno  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4675-0985","authenticated-orcid":false,"given":"Robin","family":"Jugas","sequence":"additional","affiliation":[{"name":"Center of Molecular Medicine Central European Institute of Technology, Masaryk University  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1406-2929","authenticated-orcid":false,"given":"Jan","family":"Vrbsk\u00fd","sequence":"additional","affiliation":[{"name":"Laboratory of Genetic Diagnostics, Institute of Microbiology and International Clinical Research Center, St. Anne's University Hospital  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2059-4822","authenticated-orcid":false,"given":"Martin","family":"Pail","sequence":"additional","affiliation":[{"name":"First Department of Neurology, full member of European Reference Network EpiCARE, Faculty of Medicine, Brno Epilepsy Center St. Anne's University Hospital, Masaryk University  Brno Czech 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Medicine Second Faculty of Medicine, Charles University and Motol and Homolka University Hospital, full member of European Reference Network EpiCARE  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6113-6310","authenticated-orcid":false,"given":"Lenka","family":"Krskov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine Second Faculty of Medicine, Charles University and Motol and Homolka University Hospital, full member of European Reference Network EpiCARE  Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4605-6937","authenticated-orcid":false,"given":"Adam","family":"V\u00e1cha","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Faculty of Medicine Masaryk University and St. Anne's University Hospital Brno  Brno Czech 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