Image_1_Characteristics of Genetic Variations Associated With Lennox-Gastaut Syndrome in Korean Families.tif (2.97 MB)
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posted on 20.01.2021, 04:30 authored by Jin Ok Yang, Min-Hyuk Choi, Ji-Yong Yoon, Jeong-Ju Lee, Sang Ook Nam, Soo Young Jun, Hyeok Hee Kwon, Sohyun Yun, Su-Jin Jeon, Iksu Byeon, Debasish Halder, Juhyun Kong, Byungwook Lee, Jeehun Lee, Joon-Won Kang, Nam-Soon Kim

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.

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