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. 2017 Jan 11:7:40319.
doi: 10.1038/srep40319.

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

Yimin Wang  1 , Xiaonan Du  1 , Rao Bin  2 , Shanshan Yu  2 , Zhezhi Xia  3 , Guo Zheng  4 , Jianmin Zhong  5 , Yunjian Zhang  1 , Yong-Hui Jiang  6   7   8 , Yi Wang  1   9
Affiliations

Genetic Variants Identified from Epilepsy of Unknown Etiology in Chinese Children by Targeted Exome Sequencing

Yimin Wang et al. Sci Rep. .

Erratum in

Abstract

Genetic factors play a major role in the etiology of epilepsy disorders. Recent genomics studies using next generation sequencing (NGS) technique have identified a large number of genetic variants including copy number (CNV) and single nucleotide variant (SNV) in a small set of genes from individuals with epilepsy. These discoveries have contributed significantly to evaluate the etiology of epilepsy in clinic and lay the foundation to develop molecular specific treatment. However, the molecular basis for a majority of epilepsy patients remains elusive, and furthermore, most of these studies have been conducted in Caucasian children. Here we conducted a targeted exome-sequencing of 63 trios of Chinese epilepsy families using a custom-designed NGS panel that covers 412 known and candidate genes for epilepsy. We identified pathogenic and likely pathogenic variants in 15 of 63 (23.8%) families in known epilepsy genes including SCN1A, CDKL5, STXBP1, CHD2, SCN3A, SCN9A, TSC2, MBD5, POLG and EFHC1. More importantly, we identified likely pathologic variants in several novel candidate genes such as GABRE, MYH1, and CLCN6. Our results provide the evidence supporting the application of custom-designed NGS panel in clinic and indicate a conserved genetic susceptibility for epilepsy between Chinese and Caucasian children.

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Figures

Figure 1
Figure 1
(a) A workflow of target exome sequencing and variant filtering protocol. (b) The average sequencing depth of coding exons of the representative gene TSC2 from S4. ESP6500, NHLBI Exome Sequencing Project (ESP). ExAC, Exome Aggregation Consortium.
Figure 2
Figure 2. The recurrent mutations or novel variants familial cases.
(a) A recurrent pathogenic mutation in SCN1A (c.181 C>T, p.leu61Phe) in family D1339. (b) A recurrent pathogenic mutation in PRRT2 (c.649 C>T, p.Arg217X) in family D1358.
Figure 3
Figure 3. Examples of Sanger sequencing validation and the position of sequence variants in the corresponding proteins for CDKL5 and CHD2.
Figure 4
Figure 4. A novel likely pathogenic SNP (c.1861 C>T, p.Arg621Cys) in SCN3A.
FS: febrile seizures; GEFS+: generalized epilepsy with FS plus; PKD paroxysmal kinesigenic dyskinesia.
Figure 5
Figure 5. Examples of Sanger sequencing validation and the position of sequence variants in the corresponding proteins for SLC2A1, and PLOG.
See this image and copyright information in PMC

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