Clinical and genetic spectrum of a large cohort of children with epilepsy in China.
Clinical and genetic spectrum of a large cohort of children with epilepsy in China.
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中国大量癫痫儿童的临床和遗传谱。
DOI：
10.1038/s41436-018-0091-8
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Zhou W
中科院分区：
文献类型：
--
作者：
Yang L;Kong Y;Dong X;Hu L;Lin Y;Chen X;Ni Q;Lu Y;Wu B;Wang H;Lu QR;Zhou W
癫痫儿童的基因诊断对于治疗、预后和精准医疗策略的制定具有重要意义。我们对 733 名在一岁内发病的癫痫儿童进行了外显子组测序 (ES) 或靶向测序。我们根据癫痫发作年龄将患者分组为新生儿和 1 岁之前（1-12 个月），以比较临床和遗传特征。不同癫痫发作年龄的亚组表现出不同的致病变异谱，1岁组比新生儿组更可能出现发育迟缓（p = 0.000614）。使用 2742 基因组的靶向测序的诊断率为 26.7%，ES 的诊断率为 42%。我们鉴定了 12 个基因，覆盖了 48.7% 的诊断病例。我们的数据显示，新生儿组中 41.9% 的患者和 1 岁组中 49.7% 的患者有基于分子诊断的治疗选择。如果大型医学外显子组分析或 ES 作为一级分析不可行，则该队列中 12 个最常涉及的基因以及具有治疗方案的基因应被视为癫痫发作早期诊断的基本组的一部分。遗传学结果开始通过抗癫痫药物选择和精准医学方法来改善治疗。
Genetic diagnosis for children suffering from epilepsy has important implications for treatment, prognosis, and development of precision medicine strategies. We performed exome sequencing (ES) or targeted sequencing on 733 children with epilepsy onset within the first year of life. We subgrouped our patients based on the onset age of seizure into neonatal and before 1 year (1–12 months), to compare the clinical and genetic features. The subgroups with different onset age of seizure showed different pathogenic variant spectrum, and the 1-year age group was more likely to have developmental delays than the neonate group (p = 0.000614). The diagnostic rate was 26.7% for targeted sequencing using a 2742-gene panel, and 42% for ES. We identified 12 genes, which covered 48.7% of diagnostic cases. Our data revealed that 41.9% of patients in the neonate group and 49.7% patients in the 1-year group had treatment options based on molecular diagnosis. The 12 most commonly implicated genes in this cohort and the genes with treatment options should be considered as part of the essential panel for early diagnosis of epilepsy onset, if large medical exome analyses or ES are not feasible as first-tier analysis. Genetic results are beginning to improve therapy by antiepileptic medication selections and precision medicine approaches.
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影响因子：
2
作者：
de Kovel, Carolien G. F.;Brilstra, Eva H.;van Kempen, Marjan J. A.;van't Slot, Ruben;Nijman, Isaac J.;Afawi, Zaid;De Jonghe, Peter;Djemie, Tania;Guerrini, Renzo;Hardies, Katia;Helbig, Ingo;Hendrickx, Rik;Kanaan, Moine;Kramer, Uri;Lehesjoki, Anna-Elina E.;Lemke, Johannes R.;Marini, Carla;Mei, Davide;Moller, Rikke S.;Pendziwiat, Manuela;Stamberger, Hannah;Suls, Arvid;Weckhuysen, Sarah;Koeleman, Bobby P. C.
通讯作者：
Koeleman, Bobby P. C.
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
5.6
作者：
Mercimek-Mahmutoglu, Saadet;Patel, Jaina;Snead, O. Carter
通讯作者：
Snead, O. Carter
影响因子：
5.8
作者：
McLaren, William;Pritchard, Bethan;Cunningham, Fiona
通讯作者：
Cunningham, Fiona
影响因子：
2.9
作者：
Wang, Juanjuan;Li, Yuan;Zhou, Xihui
通讯作者：
Zhou, Xihui