AUTHOR=Yang Jin Ok , Choi Min-Hyuk , Yoon Ji-Yong , Lee Jeong-Ju , Nam Sang Ook , Jun Soo Young , Kwon Hyeok Hee , Yun Sohyun , Jeon Su-Jin , Byeon Iksu , Halder Debasish , Kong Juhyun , Lee Byungwook , Lee Jeehun , Kang Joon-Won , Kim Nam-Soon TITLE=Characteristics of Genetic Variations Associated With Lennox-Gastaut Syndrome in Korean Families JOURNAL=Frontiers in Genetics VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.590924 DOI=10.3389/fgene.2020.590924 ISSN=1664-8021 ABSTRACT=

Lennox-Gastaut syndrome (LGS) is a severe type of childhood-onset epilepsy characterized by multiple types of seizures, specific discharges on electroencephalography, and intellectual disability. Most patients with LGS do not respond well to drug treatment and show poor long-term prognosis. Approximately 30% of patients without brain abnormalities have unidentifiable causes. Therefore, accurate diagnosis and treatment of LGS remain challenging. To identify causative mutations of LGS, we analyzed the whole-exome sequencing data of 17 unrelated Korean families, including patients with LGS and LGS-like epilepsy without brain abnormalities, using the Genome Analysis Toolkit. We identified 14 mutations in 14 genes as causes of LGS or LGS-like epilepsy. 64 percent of the identified genes were reported as LGS or epilepsy-related genes. Many of these variations were novel and considered as pathogenic or likely pathogenic. Network analysis was performed to classify the identified genes into two network clusters: neuronal signal transmission or neuronal development. Additionally, knockdown of two candidate genes with insufficient evidence of neuronal functions, SLC25A39 and TBC1D8, decreased neurite outgrowth and the expression level of MAP2, a neuronal marker. These results expand the spectrum of genetic variations and may aid the diagnosis and management of individuals with LGS.