{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:34:56Z","timestamp":1790750096236,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2014,10,7]],"date-time":"2014-10-07T00:00:00Z","timestamp":1412640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:p>Somatic and germline duplications or activating mutations of <jats:italic>AKT3<\/jats:italic> have been reported in patients with hemimegalencephaly and megalencephaly. We performed array comparative genomic hybridization on brain tissue and blood in 16 consecutive patients with symptomatic epilepsy due to focal or multilobar malformations of cortical development who underwent surgical treatment of epilepsy. One patient with infantile spasms and a dysplastic left frontal lobe harboured a somatic trisomy of the 1q21.1\u2010q44 chromosomal region, encompassing the <jats:italic>AKT3<\/jats:italic> gene, in the dysplastic brain tissue but not in blood and saliva. Histopathology revealed severe cortical dyslamination, a thin cortex in the premotor area with microgyri and microsulci, immature neurons with disoriented dendrites and areas of cortical heterotopia in the sub\u2010cortical white matter. These cytoarchitectural changes are close to those defining type Ib focal cortical dysplasia. Immunohistochemistry in brain specimens showed hyperactivation of the PI3K\/AKT\/mTOR pathway. These findings indicate that <jats:italic>AKT3<\/jats:italic> upregulation may cause focal malformations of cortical development. There appears to be an etiologic continuum between hemimegalencephaly and focal cortical dysplastic lesions. The extent of brain malformations due to <jats:italic>AKT3<\/jats:italic> upregulation may be related to the embryonic stage when the post\u2010zygotic gene alteration occurs.<\/jats:p>","DOI":"10.1111\/cge.12476","type":"journal-article","created":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T09:17:12Z","timestamp":1407230232000},"page":"241-247","source":"Crossref","is-referenced-by-count":66,"title":["Focal dysplasia of the cerebral cortex and infantile spasms associated with somatic 1q21.1\u2010q44 duplication including the <i><scp>AKT3<\/scp><\/i> gene"],"prefix":"10.1111","volume":"88","author":[{"given":"V.","family":"Conti","sequence":"first","affiliation":[{"name":"Pediatric Neurology and Neurogenetics Unit and Laboratories A. Meyer Children's Hospital\u00a0\u2013\u00a0University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Pantaleo","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit A. Meyer Children's Hospital\u00a0\u2013\u00a0University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Barba","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Neurogenetics Unit and Laboratories A. Meyer Children's Hospital\u00a0\u2013\u00a0University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Baroni","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine and Surgery University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Mei","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Neurogenetics Unit and Laboratories A. Meyer Children's Hospital\u00a0\u2013\u00a0University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"Buccoliero","sequence":"additional","affiliation":[{"name":"Pathology Unit A. Meyer Children's Hospital  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Giglio","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit A. Meyer Children's Hospital\u00a0\u2013\u00a0University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Giordano","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery A. Meyer Children's Hospital  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. T.","family":"Baek","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Howard Hughes Medical Institute, University of California San Diego  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. G.","family":"Gleeson","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Howard Hughes Medical Institute, University of California San Diego  La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology and Neurogenetics Unit and Laboratories A. Meyer Children's Hospital\u00a0\u2013\u00a0University of Florence  Florence Italy"},{"name":"Epilepsy and Clinical Neurophysiology Laboratory IRCCS Stella Maris Foundation  Calambrone Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,10,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02777.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.12.004"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2329"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.010"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35999"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12188"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2331"},{"key":"e_1_2_6_9_1","first-page":"43","article-title":"Expression of tuberin and hamartin in tuberous sclerosis complex\u2010associated and sporadic cortical dysplasia of Taylor's balloon cell type","volume":"46","author":"Grajkowska W","year":"2008","journal-title":"Folia Neuropathol"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt958"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2007.00059.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.5.1869-1878.2005"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e32835ef373"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2012.128"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46268"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1237758"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.2144\/000112275"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243472"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12476","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12476","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T11:58:14Z","timestamp":1696334294000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,7]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1111\/cge.12476"],"URL":"https:\/\/doi.org\/10.1111\/cge.12476","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,7]]}}}