{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:35:04Z","timestamp":1785818104089,"version":"3.56.0"},"reference-count":16,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:p>It is known that somatic activation of PI3K\u2013AKT\u2013MTOR signaling causes malformations of cortical development varying from hemimegalencephaly to focal cortical dysplasia. However, there have been few reports of fetal cases. Here we report two fetal cases of hemimegalencephaly, one associated with mosaic mutations in <jats:italic>PIK3CA<\/jats:italic> and another in <jats:italic>AKT1<\/jats:italic>. Both brains showed polymicrogyria, multiple subarachnoidal, subcortical, and subventricular heterotopia resulting from abnormal proliferation of neural stem\/progenitor cells, cell differentiation, and migration of neuroblasts. Scattered cell nests immunoreactive for phosphorylated\u2010S6 ribosomal protein (P\u2010RPS6) (Ser240\/244) were observed in the polymicrogyria\u2010like cortical plate, intermediate zone, and arachnoid space, suggesting that the PI3K\u2013AKT\u2013MTOR pathway was actually activated in these cells. Pathological analyses could shed light on the mechanisms involved in disrupted brain development in the somatic mosaicism of the PI3K\u2010AKT\u2013MTOR pathway.<\/jats:p>","DOI":"10.1111\/neup.12875","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T07:01:48Z","timestamp":1667458908000},"page":"190-196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Somatic mosaicism of the <scp>PI3K\u2010AKT\u2010MTOR<\/scp> pathway is associated with hemimegalencephaly in fetal brains"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8369-8800","authenticated-orcid":false,"given":"Kyoko","family":"Itoh","sequence":"first","affiliation":[{"name":"Department of Pathology and Applied Neurobiology Kyoto Prefectural University of Medicine, Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritsuko","family":"Pooh","sequence":"additional","affiliation":[{"name":"CRIFM Prenatal Medical Clinic, Fetal Diagnostic Center Fetal Brain Center  Osaka Japan"},{"name":"Clinical laboratory Ritz Medical Co., Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Shimokawa","sequence":"additional","affiliation":[{"name":"Clinical laboratory Ritz Medical Co., Ltd.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Fushiki","sequence":"additional","affiliation":[{"name":"Department of Pathology and Applied Neurobiology Kyoto Prefectural University of Medicine, Graduate School of Medical Science  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2011.07.008"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.010"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36836"},{"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":"10.1038\/ng.2329"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.106"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02061-5"},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/ajmg.c.31736","article-title":"Megalencephaly syndromes associated with mutations of core components of the PI3K\u2010AKT\u2013MTOR pathway: PIK3CA, PIK3R2, AKT3, and MTOR","volume":"181","author":"William B","year":"2019","journal-title":"Am J Med Genet"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12377"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2006.05.012"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1104017"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37737"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5252"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2006.00818.x"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12958"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-021-01745-0"}],"container-title":["Neuropathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.12875","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/neup.12875","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.12875","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T14:06:59Z","timestamp":1692713219000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/neup.12875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,3]]},"references-count":16,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/neup.12875"],"URL":"https:\/\/doi.org\/10.1111\/neup.12875","archive":["Portico"],"relation":{},"ISSN":["0919-6544","1440-1789"],"issn-type":[{"value":"0919-6544","type":"print"},{"value":"1440-1789","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,3]]},"assertion":[{"value":"2022-07-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}