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Objective Early-onsetepileptic encephalopathies(EEEs)is a devastating group of epilepsies which onset inthe first year of life with cognitive arrest or regression, and the majority isetiologically obscure. This disorder is genetically heterogeneous, renderingmolecular diagnosis challenging given that mutations in 18 different reported genesaccount for only approximately 12% of EEEs cases. Moreover, detectiontechnology based on Sanger sequencing is time consuming, expensive and lowdetection rate. The objective of this study was to investigate the performancecharacteristics of exon capture technology coupled with massively parallelsequencing for clinical diagnostic evaluation. Methods We designed a custom array to capture exons from 18 geneswith known involvement in EEEs and 290 genes associated with epilepsy, makingthe total number of genes 308, and sequenced the enriched material using the IlluminaHiSeq 2000 platform. A total of 50 Chinese patients were included. All patientshave a confirmed diagnosis of EEEs excluded acquired brain injury, metabolicdiseases and other known causes. ResultsEight de novo mutations and one small insertion/deletion mutations were identifiedand routinely screened with Sanger sequencing. Five of them are known pathogenicgene with unreported mutations. The rest 4 mutations were known epilepsy genesbut are the first time involving in EEEs. ConclusionThis is the first report of targeted sequencing including 308 pathogenic orrelated genes in Chinese unknown cause EEEs. We found 18% (9/50) patients carrypathogenic or likely pathogenic mutations, and 2 of them may be new EEEs pathogenicgenes in Chinese population.

Early-onset epileptic encephalopathies; targeted exomes sequence