Genetic Diagnosis Spectrum and Multigenic Burden of Exome-Level Rare Variants in a Childhood Epilepsy Cohort.
Genetic Diagnosis Spectrum and Multigenic Burden of Exome-Level Rare Variants in a Childhood Epilepsy Cohort.
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DOI：
10.3389/fgene.2021.782419
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发表时间：
2021
影响因子：
3.7
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Yao R;Zhou Y;Tang J;Li N;Yu T;He Y;Wang C;Wang J;Wang J
儿童癫痫是一种相当异质性的神经系统疾病，在世界范围内发病率很高。儿童癫痫的基因诊断提供最准确的发病证据；然而，很大一部分高度疑似病例仍未确诊。外显子组水平上罕见变异的积累作为导致儿童癫痫的多基因负担，应进一步评估。在这项回顾性分析中，利用外显子组水平测序描绘了上海儿童医学中心神经内科 294 名儿童癫痫患者的突变谱。此外，除了单基因诊断目的之外，还分析了外显子组测序数据的变异信息，以阐明与癫痫发病机制相关的罕见变异可能的多基因负担。外显子组测序诊断率达到30.61%，鉴定出6个目前未列入癫痫相关基因列表的基因。一项多基因负荷研究揭示了三重可能性，即未确诊群体中离子通道和突触基因的有害错义突变可能会导致儿童癫痫的遗传风险，而细胞生长、代谢和调节功能的基因类别的变异则没有显示出显着差异。我们的研究全面概述了中国儿童癫痫队列的遗传诊断，并为这些患者的遗传背景提供了新的见解。与离子通道和突触相关的基因中的有害错义突变最有可能在儿童癫痫中产生多基因负担。
Childhood epilepsy is a considerably heterogeneous neurological condition with a high worldwide incidence. Genetic diagnosis of childhood epilepsy provides the most accurate pathogenetic evidence; however, a large proportion of highly suspected cases remain undiagnosed. Accumulation of rare variants at the exome level as a multigenic burden contributing to childhood epilepsy should be further evaluated. In this retrospective analysis, exome-level sequencing was used to depict the mutation spectra of 294 childhood epilepsy patients from Shanghai Children’s Medical Center, Department of Neurology. Furthermore, variant information from exome sequencing data was analyzed apart from monogenic diagnostic purposes to elucidate the possible multigenic burden of rare variants related to epilepsy pathogenesis. Exome sequencing reached a diagnostic rate of 30.61% and identified six genes not currently listed in the epilepsy-associated gene list. A multigenic burden study revealed a three-fold possibility that deleterious missense mutations in ion channel and synaptic genes in the undiagnosed cohort may contribute to the genetic risk of childhood epilepsy, whereas variants in the gene categories of cell growth, metabolic, and regulatory function showed no significant difference. Our study provides a comprehensive overview of the genetic diagnosis of a Chinese childhood epilepsy cohort and provides novel insights into the genetic background of these patients. Harmful missense mutations in genes related to ion channels and synapses are most likely to produce a multigenic burden in childhood epilepsy.
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影响因子：
4.8
作者：
Jiang T;Gao J;Jiang L;Xu L;Zhao C;Su X;Shen Y;Gu W;Kong X;Yang Y;Gao F
通讯作者：
Gao F
影响因子：
--
作者：
Hebbar, Malavika;Mefford, Heather C
通讯作者：
Mefford, Heather C
中国大量癫痫儿童的临床和遗传谱。
DOI：
10.1038/s41436-018-0091-8
发表时间：
2019-03
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
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
通讯作者：
Zhou W
影响因子：
5.6
作者：
Rochtus, Anne;Olson, Heather E.;Poduri, Annapurna
通讯作者：
Poduri, Annapurna
影响因子：
4.3
作者：
Talevich E;Shain AH;Botton T;Bastian BC
通讯作者：
Bastian BC