{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:17:43Z","timestamp":1792509463753,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T00:00:00Z","timestamp":1426204800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Swiss National Foundation","award":["320030-127608"],"award-info":[{"award-number":["320030-127608"]}]},{"name":"Fondation pour la recherche sur le cerveau"},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fondation Fran\u00e7aise pour la recherche sur les \u00e9pilepsies"},{"DOI":"10.13039\/501100011900","name":"Carnot Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011900","id-type":"DOI","asserted-by":"crossref"}]},{"name":"program \u201cInvestissements d'avenir\u201d","award":["ANR-10-IAIHU-06"],"award-info":[{"award-number":["ANR-10-IAIHU-06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The <jats:italic>DEPDC5<\/jats:italic> (DEP domain\u2010containing protein 5) gene, encoding a repressor of the mTORC1 signaling pathway, has recently emerged as a major gene mutated in familial focal epilepsies. We aimed to further extend the role of <jats:italic>DEPDC5<\/jats:italic> to focal cortical dysplasias (FCDs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seven patients from 4 families with <jats:italic>DEPDC5<\/jats:italic> mutations and focal epilepsy associated with FCD were recruited and investigated at the clinical, neuroimaging, and histopathological levels. The <jats:italic>DEPDC5<\/jats:italic> gene was sequenced from genomic blood and brain DNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients had drug\u2010resistant focal epilepsy, 5 of them underwent surgery, and 1 had a brain biopsy. Electroclinical phenotypes were compatible with FCD II, although magnetic resonance imaging (MRI) was typical in only 4 cases. Histopathology confirmed FCD IIa in 2 patients (including 1 MRI\u2010negative case) and showed FCD I in 2 other patients, and remained inconclusive in the last 2 patients. Three patients were seizure\u2010free postsurgically, and 1 had a worthwhile improvement. Sequencing of blood DNA revealed truncating <jats:italic>DEPDC5<\/jats:italic> mutations in all 4 families; 1 mutation was found to be mosaic in an asymptomatic father. A brain somatic <jats:italic>DEPDC5<\/jats:italic> mutation was identified in 1 patient in addition to the germline mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Germline, germline mosaic, and brain somatic <jats:italic>DEPDC5<\/jats:italic> mutations may cause epilepsy associated with FCD, reinforcing the link between mTORC1 pathway and FCDs. Similarly to other mTORopathies, a \u201c2\u2010hit\u201d mutational model could be responsible for cortical lesions. Our study also indicates that epilepsy surgery is a valuable alternative in the treatment of drug\u2010resistant <jats:italic>DEPDC5<\/jats:italic>\u2010positive focal epilepsies, even if the MRI is unremarkable. 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