Multiple approaches of molecular and genetic analyses for pathophysiology of intractable epilepsy in childhood

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670486
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: Masayuki Itoh 国立研究開発法人国立精神・神経医療研究センター, 神経研究所疾病研究第二部, 室長 (50243407)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: てんかん / 大脳皮質形成異常 / 次世代シークエンサー / 体細胞変異

Outline of Final Research Achievements

It is known that prevalence of epilepsy is estimated about 1.0 % of peoples, and among them childhood patients occupy about 70%. The pathologies of childhood intractable epilepsy are quite a few brain malformations; those majorities are focal cortical dysplasia (FCD) and hemimegalencephaly (HME). In the present study, we revealed genetic and molecular pathomechanism of FCD and HME.
After obtained an informed consent and permitted by the committee of the institute for the study, we performed genetic analysis of 28 patients with FCD or HME by the next generation sequencer. Then, we confirmed the genetic variants by the Sanger sequencer and the currently variant ratio by the pyrosequence method. As the results, we discovered one somatic mutation patient and four germline mutation patients. Moreover, we revealed that the genetic mutations lead to form dysmorphic cells and cell migration disruption by in vivo and in vitro studies.

Free Research Field

発達病態学