Image_1_Characteristics of Genetic Variations Associated With Lennox-Gastaut Syndrome in Korean Families.tif
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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References
- https://doi.org//10.1038/nmeth0410-248
- https://doi.org//10.1002/ana.24457
- https://doi.org//10.1038/nature12439
- https://doi.org//10.1007/s10072-017-3188-y
- https://doi.org//10.1177/0883073809348355
- https://doi.org//10.1016/j.expneurol.2009.10.011
- https://doi.org//10.12688/f1000research.10588.1
- https://doi.org//10.1002/stem.1990
- https://doi.org//10.1111/j.1528-1167.2011.03177.x
- https://doi.org//10.1101/gr.092619.109
- https://doi.org//10.3389/fneur.2017.00505
- https://doi.org//10.3389/fgene.2018.00020
- https://doi.org//10.1073/pnas.1316294111
- https://doi.org//10.1016/j.eplepsyres.2017.11.015
- https://doi.org//10.1038/s41467-018-02927-4
- https://doi.org//10.1016/j.conb.2017.02.001
- https://doi.org//10.3389/fneur.2018.00298
- https://doi.org//10.1016/j.modgep.2003.10.004
- https://doi.org//10.3389/fnmol.2017.00402
- https://doi.org//10.1002/jnr.23074
- https://doi.org//10.7759/cureus.3134
- https://doi.org//10.1093/nar/gku1363
- https://doi.org//10.1016/j.tins.2016.11.008
- https://doi.org//10.1093/brain/awz391
- https://doi.org//10.1016/j.yebeh.2014.02.005
- https://doi.org//10.1016/j.eplepsyres.2013.01.009
- https://doi.org//10.1016/j.ajhg.2016.04.008
- https://doi.org//10.1101/gr.107524.110
- https://doi.org//10.1016/j.neulet.2016.04.050
- https://doi.org//10.1038/sj.emboj.7601911
- https://doi.org//10.1111/epi.13135
- https://doi.org//10.1038/mp.2016.109
- https://doi.org//10.1038/gim.2015.30
- https://doi.org//10.1038/nmeth0810-575
- https://doi.org//10.1093/nar/gks539
- https://doi.org//10.1016/j.eplepsyres.2009.09.022
- https://doi.org//10.1523/JNEUROSCI.3432-15.2016
- https://doi.org//10.1113/jphysiol.2011.220236
- https://doi.org//10.1038/nn.3947
- https://doi.org//10.1111/j.1742-4658.2009.07367.x
- https://doi.org//10.1111/epi.12800
- https://doi.org//10.1111/j.1471-4159.2011.07257.x
- https://doi.org//10.1111/cge.13203
- https://doi.org//10.3389/fncel.2013.00080
- https://doi.org//10.1016/j.seizure.2016.11.030
- https://doi.org//10.1093/nar/gkq603
- https://doi.org//10.1111/epi.13560
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Categories
- Gene and Molecular Therapy
- Biomarkers
- Genetics
- Genetically Modified Animals
- Developmental Genetics (incl. Sex Determination)
- Epigenetics (incl. Genome Methylation and Epigenomics)
- Gene Expression (incl. Microarray and other genome-wide approaches)
- Livestock Cloning
- Genome Structure and Regulation
- Genetic Engineering
- Genomics