NEXT GENERATION WHOLE EXOME SEQUENCING IN THE GENETIC DIAGNOSIS OF DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY

The identification of causative mutations associated with developmental epileptic encephalopathies (DEE) is useful for clinical diagnosis. The applications of next-generation sequencing (NGS) technologies including targeted gene panel and whole-exome sequencing (WES) highlight the striking impact on medicine. During recent years, we tried to find the pathogenetic causes among DEE patients through WES. A series of 20 (11 males and 9 females) patients exhibiting DEE with seizure onset within the first 2 years of life were collected and their genetic profiles were analyzed with WES. They were aged 1 month to 23 years. Mutations were found in 13 (7 boys and 6 girls) probands; The overall mutation identification rate via WES was 65%. Three (23%) mutations involve ion channels, including each in GABRG2, SCN1A, and SCN2A. The other 10 (76.9%) mutations include CDKL5, KIDINS220, QARS1, TUBB2B, TUBA1A, IQSEC2, FOXP1, E1F2AK2, and two MECP2. Eleven (84.6%) of the identified mutations were de novo and one (15.4%) was autosomal recessive inheritance. Of 6 patients with negative gene panel study before, 3 became positive by WES study. Four novel identified mutations (KIDINS220, QARS1, IQSEC2, FOXP1) were not included in our previous gene panel. Our data showed the genetic heterogeneity of DEE. Using WES, the mutation identification rate was 65%, higher than 29.5% of our previous panel study. The use of NGS technologies will be the future of genetic diagnosis. As the price continues to decrease, they will eventually be integrated into the diagnostic profile and provide a valid option for clinical use.
Keywords: Developmental epileptic encephalopathies, next-generation sequencing, targeted gene panel, genetic diagnosis