{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:15:31Z","timestamp":1791396931237,"version":"4.3.3"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010270","name":"Capital Health Research and Development of Special Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010270","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Focal cortical dysplasia (FCD) is a major cause of drug\u2010resistant paediatric epilepsy and is amenable to successful neurosurgical resection. FCD ILAE Type IIb is the most common FCD subtype, and brain somatic mutations affecting the mTOR pathway play a major pathogenic role. The aim of this study was to comprehensively describe the genotype\u2013phenotype association of 20 patients with histopathologically confirmed FCDIIb using next generation sequencing (NGS) of paired blood\u2013brain samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical and neuropathological data were retrospectively reviewed from the hospital archive. The NGS panel included 11 mTOR\u2010pathway\u2010related genes with maximum coverage of 2000\u00d7. The detected variants were validated by digital droplet PCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Pathogenic\n                      <jats:italic>MTOR<\/jats:italic>\n                      variants were identified in 10 patients (50%). Further comparison with\n                      <jats:italic>MTOR<\/jats:italic>\n                      \u2010wildtype FCDIIb suggested a profound genotype\u2013phenotype association characterised by (1) a non\u2010temporal lobe lesion on MRI, (2) a larger lesion volume occupying grey and white matter (3.032\u2009\u00b1\u20091.859\u2009cm\n                      <jats:sup>3<\/jats:sup>\n                      vs 1.110\u2009\u00b1\u20090.856\u2009cm\n                      <jats:sup>3<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.014), (3) more balloon cells (50.20\u2009\u00b1\u200914.40\u2009BC\/mm\n                      <jats:sup>2<\/jats:sup>\n                      vs 31.64\u2009\u00b1\u200930.56\u2009BC\/mm\n                      <jats:sup>2<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.099) and dysmorphic neurons (48.72\u2009\u00b1\u200919.47DN\/mm\n                      <jats:sup>2<\/jats:sup>\n                      vs 15.28\u2009\u00b1\u200913.95DN\/mm\n                      <jats:sup>2<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.000) and (4) a positive correlation between VAF and the lesion volume (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.802,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study identified frequent\n                      <jats:italic>MTOR<\/jats:italic>\n                      mutations in the cell\u2010rich FCDIIb phenotype, clinically characterised by a non\u2010temporal location and large lesion volume. Comprehensive genotype\u2013phenotype associations will help us further explore and define the broad spectrum of FCD lesions to make more targeted therapies available in the realm of epileptology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12874","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T02:06:52Z","timestamp":1671674812000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The clinico\u2010pathological characterisation of focal cortical dysplasia type IIb genetically defined by\n                    <i>MTOR<\/i>\n                    mosaicism"],"prefix":"10.1111","volume":"49","author":[{"given":"Yajie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology, Xuanwu Hospital Capital Medical University  Beijing China"},{"name":"Clinical Research Center for Epilepsy Capital Medical University  Beijing 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