{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:27:23Z","timestamp":1792121243969,"version":"4.4.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Suh Kyungbae Foundation"},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean government\u2019s Ministry of Science and ICT","award":["2019R1A3B2066619"],"award-info":[{"award-number":["2019R1A3B2066619"]}]},{"name":"Ministry of Health and Welfare of the Republic of Korea"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Somatic mosaicism in a fraction of brain cells causes neurodevelopmental disorders, including childhood intractable epilepsy. However, the threshold for somatic mosaicism leading to brain dysfunction is unknown. In this study, we induced various mosaic burdens in focal cortical dysplasia type II (FCD II) mice, featuring mTOR somatic mosaicism and spontaneous behavioural seizures.<\/jats:p>\n                  <jats:p>The mosaic burdens ranged from approximately 1000 to 40 000 neurons expressing the mTOR mutant in the somatosensory or medial prefrontal cortex. Surprisingly, approximately 8000\u20139000 neurons expressing the MTOR mutant, extrapolated to constitute 0.08%\u20130.09% of total cells or roughly 0.04% of variant allele frequency in the mouse hemicortex, were sufficient to trigger epileptic seizures. The mutational burden was correlated with seizure frequency and onset, with a higher tendency for electrographic inter-ictal spikes and beta- and gamma-frequency oscillations in FCD II mice exceeding the threshold. Moreover, mutation-negative FCD II patients in deep sequencing of their bulky brain tissues revealed somatic mosaicism of the mTOR pathway genes as low as 0.07% in resected brain tissues through ultra-deep targeted sequencing (up to 20 million reads). Thus, our study suggests that extremely low levels of somatic mosaicism can contribute to brain dysfunction.<\/jats:p>","DOI":"10.1093\/brain\/awae190","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T17:46:16Z","timestamp":1718819176000},"page":"2983-2990","source":"Crossref","is-referenced-by-count":17,"title":["Threshold of somatic mosaicism leading to brain dysfunction with focal epilepsy"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9817-6726","authenticated-orcid":false,"given":"Jintae","family":"Kim","sequence":"first","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST) , Daejeon 34141 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Min","family":"Park","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST) , Daejeon 34141 ,","place":["Republic of Korea"]},{"name":"SoVarGen Co., Ltd. , Daejeon 34051 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Yong","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Neurology, Baylor College of Medicine , Houston 77030 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ara","family":"Ko","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST) , Daejeon 34141 ,","place":["Republic of Korea"]},{"name":"Department of Pediatrics, Yonsei University College of Medicine , Seoul 03722 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoon-Chul","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Yonsei 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