BMB Rep. 2016; 49(2): 71-72  
Brain somatic mutations in MTOR leading to focal cortical dysplasia
Jae Seok Lim & Jeong Ho Lee*
Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Korea
Correspondence to: E-mail:
Received: January 15, 2016; Published online: February 28, 2016.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

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.
Keywords: Focal cortical dysplasia, Mechanistic target of rapamycin, Mouse model, Somatic mutation

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