authors: D'Gama AM., Geng Y., Couto JA., Martin B., Boyle EA., LaCoursiere CM., Hossain A., Hatem NE., Barry BJ., Kwiatkowski DJ., Vinters HV., Barkovich AJ., Shendure J., Mathern GW., Walsh GA., Poduri A.
Ann Neurol. 2015 Apr;77(4):720-5. doi: 10.1002/ana.24357.
Focalmalformations of cortical development, including focalcortical dysplasia (FCD) and hemimegalencephaly (HME), are important causes of intractable childhood epilepsy. Using targeted and exome sequencing on DNA from resected brain samples and nonbrain samples from 53 patients with FCD or HME, we identified pathogenic germline and mosaic mutations in multiple PI3K/AKT pathway genes in 9 patients, and a likely pathogenic variant in 1 additional patient. Our data confirm the association of DEPDC5 with sporadic FCD but also implicate this gene for the first time in HME. Our findings suggest that modulation of the mammalian target of rapamycinpathway may hold promise for malformation-associated epilepsy.