Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy(nature medicine VOLUME 21 | NUMBER 4 | APRIL 2015.)

報告日期: 2015/11/17
報告時間: 5:10/6:00
報告學生: 陳柏源
講評老師: 楊尚訓
附件下載: 下載[1524-1443055189-1.pdf] 

 Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy

Jae Seok Lim, Woo-il Kim, Hoon-Chul Kang, Se Hoon Kim, Ah Hyung Park, Eun Kyung Park, Young-Wook Cho, Sangwoo Kim, Ho Min Kim, Jeong A Kim, Junho Kim, Hwanseok R/hee, Seok-Gu Kang, Heung Dong Kim, Daesoo Kim, Dong-Seok Kim & Jeong Ho Lee

Nature medicine, April 2015

Speaker: Po-yuan Chen(陳柏源)                Time: 17:10-18:00, 15/11/17

Commentator: Dr. Shang-Hsun Yang              


    Focal cortical dysplasia type II (FCDII) is an occasionally maldevelopment of cerebral cortex, which is mainly caused by abnormal migration of neuron cell, dyslamination, or balloon cell formation1. Some FCDII patients who suffered from refractory and intractable seizure failed to identify the cause of disease. Recently, it has been hypothesized that somatic mutation in brain affected area lead to FCDII. The authors used deep whole-exome sequencing (WES) and site-specific amplicon sequencing to exam the DNA from four patients’ affected brain area and blood. Successfully, they uncovered a low frequency somatic mutation of mTOR c.7280T>C (p.Leu2427Pro) in two patients. Deep amplicon sequencing in 73 FCDII patients also revealed 15.6% of the subjects with eight different somatic mutations which was identified to induce mTOR hyperactivation and were further confirmed by transfect mutation mTOR into 293T cell. In utero electroporation was used to deliver mutation mTOR into mice leading to neuron cell abnormal migration and spontaneous seizure. mTOR inhibitor, rapamycin, was treated and successfully reduced the abnormal enlarged of neuron cell and seizure phenotype. This study carried out an evidence that somatic mutation of mTOR would cause FCDII and there is a possibility treatment of FCDII by mTOR inhibition.


1.     Joanna Kabat and Przemysław Król. Focal cortical dysplasia – review. Polish Journal of Radiology. 2012, 77(2):35-43