{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:57:27Z","timestamp":1789070247520,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["V1041T"],"award-info":[{"award-number":["V1041T"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Brain development and subsequent brain function are highly sensitive to genetic mutations, which can result in severe neurodevelopmental malformations. Alterations in PTEN signaling cause a spectrum of developmental malformations and neurological diseases including epilepsy. To date, a detailed understanding of the neuropathological underpinnings of\n                    <jats:italic>PTEN<\/jats:italic>\n                    \u2010associated brain malformations, particularly in fetuses, is missing. We have thus investigated a fetal case of hemimegalencephaly (HME), which is a rare disorder characterized by hemispheric overgrowth, developmental delay, and epileptic seizures. Our assessment of the male fetus includes genetic, radiologic, and histologic features and provides a comprehensive characterization of the cellular alterations in HME together with a genotypic correlation. Genetic analyses uncovered that hemispheric overgrowth was caused by a somatic second hit resulting in biallelic\n                    <jats:italic>PTEN<\/jats:italic>\n                    alteration in the affected brain tissue, although the unaffected hemisphere carried the same\n                    <jats:italic>PTEN<\/jats:italic>\n                    variant as the heterozygous germline variant. Based on the latter, we interpret that the\n                    <jats:italic>PTEN<\/jats:italic>\n                    mutation is not a dominant\u2010negative variant. Within the outer subventricular zone of the enlarged cortex, we found small nodular heterotopias, which can be origins of focal epileptic seizures. Cell type\u2010specific marker stainings revealed that the heterotopias consisted exclusively of SATB2\n                    <jats:sup>+<\/jats:sup>\n                    glutamatergic projection neurons. Altogether, our analyses and findings contribute to a deeper understanding of the pathomechanisms of a novel\n                    <jats:italic>PTEN<\/jats:italic>\n                    variant driving a severe brain malformation.\n                  <\/jats:p>","DOI":"10.1002\/epi.70088","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:39:43Z","timestamp":1767627583000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A novel\n                    <scp>\n                      <i>PTEN<\/i>\n                    <\/scp>\n                    variant causing hemimegalencephaly and focal nodular heterotopias in the developing human brain"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3050-1550","authenticated-orcid":false,"given":"Franziska","family":"Fazekas","sequence":"first","affiliation":[{"name":"Department of Neurology, Division of Neuropathology and Neurochemistry Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3488-4920","authenticated-orcid":false,"given":"Amit","family":"Haboosheh","sequence":"additional","affiliation":[{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna  Vienna Austria"},{"name":"Department of Biomedical Imaging and Image\u2010Guided Therapy, Division of Neuroradiology and Musculoskeletal Radiology Medical University of Vienna  Vienna Austria"},{"name":"Department of Radiology Hadassah Medical Center  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3203-1375","authenticated-orcid":false,"given":"Bernhard","family":"Hennebichler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Neuropathology and Neurochemistry Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8875-7304","authenticated-orcid":false,"given":"Thomas","family":"Roetzer\u2010Pejrimovsky","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Neuropathology and Neurochemistry Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5725-9270","authenticated-orcid":false,"given":"Julia","family":"Binder","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Obstetrics and Feto\u2010Maternal Medicine, and Comprehensive Center for Pediatrics Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4021-1262","authenticated-orcid":false,"given":"Theresa","family":"Reischer","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Obstetrics and Feto\u2010Maternal Medicine, and Comprehensive Center for Pediatrics Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1459-4802","authenticated-orcid":false,"given":"Mateja","family":"Pfeifer","sequence":"additional","affiliation":[{"name":"Medical University of Vienna Center for Pathobiochemistry and Genetics, Institute of Medical Genetics  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-3226","authenticated-orcid":false,"given":"Anke","family":"Scharrer","sequence":"additional","affiliation":[{"name":"Department of Pathology Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7635-3721","authenticated-orcid":false,"given":"Christof","family":"Worda","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Obstetrics and Feto\u2010Maternal Medicine, and Comprehensive Center for Pediatrics Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5929-1285","authenticated-orcid":false,"given":"Tina","family":"Linder","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Obstetrics and Feto\u2010Maternal Medicine, and Comprehensive Center for Pediatrics Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4628-9052","authenticated-orcid":false,"given":"Alex","family":"Farr","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Obstetrics and Feto\u2010Maternal Medicine, and Comprehensive Center for Pediatrics Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5769-1100","authenticated-orcid":false,"given":"Romana","family":"H\u00f6ftberger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Neuropathology and Neurochemistry Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2948-4187","authenticated-orcid":false,"given":"Ellen","family":"Gelpi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Division of Neuropathology and Neurochemistry Medical University of Vienna  Vienna Austria"},{"name":"Comprehensive Center for Clinical Neurosciences and Mental Health Medical University of Vienna  Vienna 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Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.add7046"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-022-00572-x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12377"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv045"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/neup.12875"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.5238"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebcr.2017.02.002"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae253"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab173"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23636"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.25243"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13185"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2023.11.004"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2899-04.2005"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.11.016"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2023.102677"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1954"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a036780"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.11.017"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18148"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/122.2.219"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70088","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi.70088","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70088","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T13:05:06Z","timestamp":1776431106000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi.70088"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,5]]},"references-count":21,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/epi.70088"],"URL":"https:\/\/doi.org\/10.1002\/epi.70088","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,5]]},"assertion":[{"value":"2025-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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