[SP3-3A-5] Molecular Diagnosis of Epileptic Encephalopathies Using Targeted Next Generation Sequencing (NGS)
Epileptic encephalopathies are highly heterogeneous and phenotypical disorders with different underlying genetic defects. Finding the genetic basis of epileptic encephalopathies can be valuable not only for diagnosis but also for guiding treatment and providing disease prognosis. The advance development of next generation DNA sequencing (NGS) techniques greatly improve the efficacy of mutational screening for human diseases in a timely and cost effective ways, and has been shown to be beneficial in molecular diagnosis of epileptic disorders. We applied targeted Next Generation Sequencing (NGS) of a 90 gene panel as a diagnostic tool to analyze the genetic basis in children with different epileptic encephalopathies. After screening 44 probands (16 males and 28 female) and analyzing available parents and siblings, nine (1 male and 8 females) were found to have mutations in ion channels, including SCN1A, SCN2A, SCN8A, KCNB1 and KCNT1. Four (1 male and 3 females) exhibit variations in non-channel genes, including CDKL5, STXBP1 and SYNGAP1. Among them eight are missense mutations, three are frameshift mutations and another two are in-frame deletion and nonsense mutation. So far, six of them were confirmed to be de novo mutations and the estimated detection efficacy is about 29.5%.