{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:20:25Z","timestamp":1788805225446,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017643","name":"Saastamoisen s\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017643","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epileptic Disorders"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Recessive <jats:italic>LAMC3<\/jats:italic> mutations are recognized to cause epilepsy with cortical malformations characterized by polymicrogyria and pachygyria. The objective of this study was to describe the clinical picture and epilepsy phenotype of four patients with a previously undescribed <jats:italic>LAMC3<\/jats:italic> variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>All epilepsy patients treated in Kuopio Epilepsy Center (located in Kuopio, Finland) are offered the possibility to participate in a scientific study investigating biomarkers in epilepsy (Epibiomarker study). We have collected a comprehensive database of the study population, and are currently re\u2010evaluating our database regarding the patients with developmental and\/or epileptic encephalopathy (DEE). If the etiology of epilepsy remains unknown in the clinical setting, we are performing whole exome sequencing to recognize the genetic causes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among our study population of 323 DEE patients we recognized three patients with similar homozygous <jats:italic>LAMC3<\/jats:italic> c.1866del (p.(Phe623Serfs*10)) frameshift variant and one patient with a compound heterozygous mutation where the same frameshift variant was combined with an intronic <jats:italic>LAMC3<\/jats:italic> c.4231\u201012C&gt;G variant on another allele. All these patients have severe epilepsy and either bilateral agyria\u2010pachygyria or bilateral polymicrogyria in their clinical MRI scanning. Cortical malformations involve the occipital lobes in all our patients. Epilepsy phenotype is variable as two of our patients have DEE with epileptic spasms progressing to Lennox\u2013Gastaut syndrome and intellectual disability. The other two patients have focal epilepsy without marked cognitive deficit. The four patients are unrelated. <jats:italic>LAMC3<\/jats:italic> c.1866del p.(Phe623Serfs*10) frameshift variant is enriched in the Finnish population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Only a few patients with epilepsy caused by <jats:italic>LAMC3<\/jats:italic> homozygous or compound heterozygous mutations have been described in the literature. To our knowledge, the variants discovered in our patients have not previously been published. Clinical phenotype appears to be more varied than previously assumed and patients with a milder phenotype and normal cognition have probably remained unrecognized.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epd2.20244","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T13:35:38Z","timestamp":1715952938000},"page":"498-509","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel <scp><i>LAMC3<\/i><\/scp> pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy"],"prefix":"10.1002","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8582-2369","authenticated-orcid":false,"given":"Anni","family":"Saarela","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Kuopio Epilepsy Center. Kuopio University Hospital. Full Member of ERN EpiCARE.  Kuopio Finland"},{"name":"Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskari","family":"Timonen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarkko","family":"Kirjavainen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Kuopio Epilepsy Center. Kuopio University Hospital. Full Member of ERN EpiCARE.  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawu","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katri","family":"Silvennoinen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kuopio Epilepsy Center Kuopio University Hospital. Full Member of ERN EpiCARE  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esa","family":"Mervaala","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"},{"name":"Department of Clinical Neurophysiology, Kuopio Epilepsy Center Kuopio University Hospital. Full Member of ERN EpiCARE  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reetta","family":"K\u00e4lvi\u00e4inen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine University of Eastern Finland  Kuopio Finland"},{"name":"Department of Neurology, Kuopio Epilepsy Center Kuopio University Hospital. Full Member of ERN EpiCARE  Kuopio Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcaa221"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.2363"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16854"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa174"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcad213"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.22057"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.836"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000680"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.990350"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002404"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.616761\/full"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61846"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-017-0534-4"},{"issue":"1","key":"e_1_2_8_15_1","first-page":"1","article-title":"Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia","volume":"14","author":"De Angelis C","year":"2021","journal-title":"BMC Med Genet"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.05.001"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13670"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_21_1","unstructured":"Blueprint Genetics.Bioinformatics process.2023[cited 2023 Nov 9]. 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