{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T07:47:09Z","timestamp":1781164029216,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRONAS","award":["25000.069257\/2015-00"],"award-info":[{"award-number":["25000.069257\/2015-00"]}]},{"name":"PRONAS","award":["R00HD111686"],"award-info":[{"award-number":["R00HD111686"]}]},{"name":"PRONAS","award":["R21MH134401"],"award-info":[{"award-number":["R21MH134401"]}]},{"name":"NIH\/NICHD","award":["25000.069257\/2015-00"],"award-info":[{"award-number":["25000.069257\/2015-00"]}]},{"name":"NIH\/NICHD","award":["R00HD111686"],"award-info":[{"award-number":["R00HD111686"]}]},{"name":"NIH\/NICHD","award":["R21MH134401"],"award-info":[{"award-number":["R21MH134401"]}]},{"DOI":"10.13039\/100000025","name":"NIH\/NIMH","doi-asserted-by":"publisher","award":["25000.069257\/2015-00"],"award-info":[{"award-number":["25000.069257\/2015-00"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"NIH\/NIMH","doi-asserted-by":"publisher","award":["R00HD111686"],"award-info":[{"award-number":["R00HD111686"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"NIH\/NIMH","doi-asserted-by":"publisher","award":["R21MH134401"],"award-info":[{"award-number":["R21MH134401"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Focal cortical dysplasia type III (FCDIII) is a rare and complex condition associated with drug-resistant epilepsy and often characterized by cortical lamination abnormalities, along with a variety of neoplasms and vascular abnormalities. Objectives: This study aimed to elucidate the genetic architecture underlying FCDIII through the use of whole-exome sequencing (WES) of brain and peripheral blood samples from 19 patients who had been diagnosed with FCDIII. Methods: Variants were identified through a series of machine-learning-based detection and functional prediction methods and were not previously associated with FCDIII. Mosaic fraction scores of these variants validated the variants\u2019 pathogenicity, and in silico and gene ontology enrichment analyses demonstrated that these variants had severe destabilizing effects on protein structure. Results: We reported ten novel pathogenic somatic missense and loss of function variants across eight genes, including CNTNAP2, ACY1, SERAC1, and BRAF. Genetic alterations were linked to clinical manifestations, such as encephalopathies and intellectual disabilities, thereby emphasizing their role as molecular drivers of FCDIII. Conclusions: We demonstrated that next-generation sequencing-based mosaic variant-calling pipelines are useful for the genetic diagnosis of FCDIII, opening up avenues for targeted therapies, yet further research is required to validate these findings and examine their therapeutic implications.<\/jats:p>","DOI":"10.3390\/genes16040421","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T04:21:01Z","timestamp":1743481261000},"page":"421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of Novel Mosaic Variants in Focal Epilepsy-Associated Patients\u2019 Brain Lesions"],"prefix":"10.3390","volume":"16","author":[{"given":"Camila Ara\u00fajo Bernardino","family":"Garcia","sequence":"first","affiliation":[{"name":"Department of Surgery and Anatomy, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (USP), Ribeirao Preto 14049-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Zubair","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Volpon","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Surgery and Anatomy, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (USP), Ribeirao Preto 14049-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Hyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian Alfred","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2212-7796","authenticated-orcid":false,"given":"Valentina","family":"Stanley","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of California, San Diego, CA 92093, USA"},{"name":"Rady Children\u2019s Institute for Genomic Medicine, San Diego, CA 92123, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee D.","family":"George","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of California, San Diego, CA 92093, USA"},{"name":"Rady Children\u2019s Institute for Genomic Medicine, San Diego, CA 92123, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph G.","family":"Gleeson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of California, San Diego, CA 92093, USA"},{"name":"Rady Children\u2019s Institute for Genomic Medicine, San Diego, CA 92123, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9lio Rubens","family":"Machado","sequence":"additional","affiliation":[{"name":"Department of Surgery and Anatomy, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (USP), Ribeirao Preto 14049-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0219-0023","authenticated-orcid":false,"given":"Xiaoxu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1080\/14737175.2021.1915135","article-title":"Focal cortical dysplasia: An update on diagnosis and treatment","volume":"21","author":"Guerrini","year":"2021","journal-title":"Expert Rev. 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