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

• Published in: Scientific reports 2017-01, Vol.7 (1), p.40319-40319, Article 40319
• Main Authors: Wang, Yimin, Du, Xiaonan, Bin, Rao, Yu, Shanshan, Xia, Zhezhi, Zheng, Guo, Zhong, Jianmin, Zhang, Yunjian, Jiang, Yong-hui, Wang, Yi
• Format: Article
• Language: English
• Subjects: 631/208/135; 631/208/514/2254; Base Sequence; Child; Children; Copy number; Epilepsy; Epilepsy - genetics; Etiology; Female; Genetic factors; Genetic Predisposition to Disease; Genetic variance; Genetic Variation; Genomics; Humanities and Social Sciences; Humans; Infant; Male; multidisciplinary; Mutation - genetics; Pedigree; Polymorphism, Single Nucleotide - genetics; Reproducibility of Results; Science; Sodium channels (voltage-gated); Tuberous Sclerosis Complex 2; Whole Exome Sequencing
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep40319

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.