Brain somatic mutations in MTOR leading to focal cortical dysplasia
Brain somatic mutations in MTOR leading to focal cortical dysplasia
BMB Reports. 2016. Feb, 49(2): 71-72
Copyright © 2016, Korean Society for Biochemistry and Molecular Biology
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  • Received : January 15, 2016
  • Published : February 29, 2016
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Jae Seok Lim
Jeong Ho Lee

Focal cortical dysplasia type II (FCDII) is a focal malformation of the developing cerebral cortex and the major cause of intractable epilepsy. However, since the molecular genetic etiology of FCD has remained enigmatic, the effective therapeutic target for this condition has remained poorly understood. Our recent study on FCD utilizing various deep sequencing platforms identified somatic mutations in MTOR (existing as low as 1% allelic frequency) only in the affected brain tissues. We observed that these mutations induced hyperactivation of the mTOR kinase. In addition, focal cortical expression of mutant MTOR using in utero electroporation in mice, recapitulated the neuropathological features of FCDII, such as migration defect, cytomegalic neuron and spontaneous seizures. Furthermore, seizures and dysmorphic neurons were rescued by the administration of mTOR inhibitor, rapamycin. This study provides the first evidence that brain somatic activating mutations in MTOR cause FCD, and suggests the potential drug target for intractable epilepsy in FCD patients. [BMB Reports 2016; 49(2): 71-72]
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This work was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A121070, HI13C0208 to J.H.L.), the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2013M3C7A1056564 to J.H.L.), the KAIST Future Systems Healthcare Project from the Ministry of Science, ICT and Future Planning (to J.H.L.).