Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study

作者：Dongfang Zou, Lin Wang, Jianxiang Liao, Hongdou Xiao, Jing Duan, Tongda Zhang, Jianbiao Li, Zhenzhen Yin, Jing Zhou, Haisheng Yan, Yushan Huang, Nianji Zhan, Ying Yang, Jingyu Ye, Fang Chen, Shida Zhu, Feiqiu Wen, Jian Guo · 发表于：Brain · 年份：2021 · DOI：10.1093/brain/awab233 · 被引用次数：38 · 研究领域：Genomics and Rare Diseases、Genetics and Neurodevelopmental Disorders、Epilepsy research and treatment

The aim of this study is to evaluate the diagnostic value of genome sequencing in children with epilepsy, and to provide genome sequencing-based insights into the molecular genetic mechanisms of epilepsy to help establish accurate diagnoses, design appropriate treatments and assist in genetic counselling. We performed genome sequencing on 320 Chinese children with epilepsy, and interpreted single-nucleotide variants and copy number variants of all samples. The complete pedigree and clinical data of the probands were established and followed up. The clinical phenotypes, treatments, prognoses and genotypes of the patients were analysed. Age at seizure onset ranged from 1 day to 17 years, with a median of 4.3 years. Pathogenic/likely pathogenic variants were found in 117 of the 320 children (36.6%), of whom 93 (29.1%) had single-nucleotide variants, 22 (6.9%) had copy number variants and two had both single-nucleotide variants and copy number variants. Single-nucleotide variants were most frequently found in SCN1A (10/95, 10.5%), which is associated with Dravet syndrome, followed by PRRT2 (8/95, 8.4%), which is associated with benign familial infantile epilepsy, and TSC2 (7/95, 7.4%), which is associated with tuberous sclerosis. Among the copy number variants, there were three with a length <25 kilobases. The most common recurrent copy number variants were 17p13.3 deletions (5/24, 20.8%), 16p11.2 deletions (4/24, 16.7%), and 7q11.23 duplications (2/24, 8.3%), which are associate...