{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T15:58:12Z","timestamp":1780934292418,"version":"3.54.1"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"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":["Epileptic Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Temporal lobe epilepsy (TLE) is the most common focal epilepsy, yet the genetic mechanisms underlying its development remain incompletely understood. The sodium channel gene SCN1A, known to be involved in several epilepsy syndromes including Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+), has recently been investigated for its potential role in TLE. This systematic review aimed to synthesize evidence on the role of SCN1A variants in the pathogenesis, clinical features, and treatment outcomes of TLE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive literature search of PubMed, Scopus, Web of Science, and the Cochrane Library was conducted up to September 2024. Twenty\u2010six eligible studies, including clinical, molecular, and preclinical investigations, were analyzed to assess associations between SCN1A mutations or polymorphisms and TLE phenotypes, with particular focus on genetic, electrophysiological, and therapeutic findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Clinical studies reported both common polymorphisms (rs3812718, rs7587026) and rare familial variants (M145T, K1270T) in patients with mesial TLE with hippocampal sclerosis (MTLE\u2010HS) and drug resistance. Transcriptomic and electrophysiological analyses of resected hippocampal tissue suggested altered SCN1A expression and possible interneuron dysfunction. Experimental models further indicated that SCN1A dysregulation may influence hippocampal excitability and seizure thresholds, while sodium channel modulators such as carbamazepine were reported to normalize aberrant expression patterns and reduce epileptiform activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Current evidence suggests that SCN1A may act as a genetic modifier contributing to TLE susceptibility, pharmacoresistance, and clinical heterogeneity in certain contexts. Integration of genetic and molecular data may support improved phenotypic characterization and individualized management in selected patients. However, larger and well\u2010designed studies incorporating multi\u2010omics and longitudinal data are required to clarify the mechanistic and clinical relevance of SCN1A in TLE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epd2.70303","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T15:05:51Z","timestamp":1780931151000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of\n                    <scp>SCN1A<\/scp>\n                    mutations in temporal lobe epilepsy: Genetic insights and clinical implications"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1115-4610","authenticated-orcid":false,"given":"Bassel","family":"Alrabadi","sequence":"first","affiliation":[{"name":"Faculty of Medicine Jordan University of Science and Technology  Irbid 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