Multi-gene panel testing in Korean patients with common genetic generalized epilepsy syndromes.
Multi-gene panel testing in Korean patients with common genetic generalized epilepsy syndromes.
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DOI：
10.1371/journal.pone.0199321
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Lee M
中科院分区：
文献类型：
--
作者：
Lee CG;Lee J;Lee M
常见遗传性全身性癫痫综合征的遗传异质性经常被考虑。本研究利用新一代测序的多基因组测试，对常见遗传性全身性癫痫综合征的潜在候选基因或易感基因进行了集中分析。这项研究包括青少年肌阵挛性癫痫、青少年失神性癫痫和单纯全身强直阵挛性癫痫发作的患者。我们根据美国医学遗传学和基因组学学院指南确定了致病变异，并使用病例对照关联分析和家族病例的家族分析确定了易感性变异。共纳入57例患者，其中散发病例51例，家族性病例6例。鉴定出 16 个不同基因的 22 个致病变异和可能致病变异。 CACNA1H 是最常观察到的单基因。在 32% 的变异中观察到电压门控 Ca2+ 通道基因的变异，包括 CACNA1A、CACNA1G 和 CACNA1H (n = 7/22)。使用病例对照关联分析识别易感性变异的分析表明，KCNMA1 c.400G>C 与常见的遗传性全身性癫痫综合征相关。通过家族分析确定，只有 1 个家族（A 家族）在 CACNA1H 上表现出候选致病性变异 p.(Arg788His)。这项研究在大约四分之一的患者 (n = 16/57) 中发现了候选基因变异，并且在每个患者中平均发现了 2.8 个变异。结果强化了常见 GGE 综合征的多基因疾病具有非常高的基因座和等位基因异质性。此外，电压门控 Ca2+ 通道被认为是常见遗传性全身性癫痫综合征的重要贡献者。这项研究扩展了我们对常见遗传性全身性癫痫综合征的全面理解。
Genetic heterogeneity of common genetic generalized epilepsy syndromes is frequently considered. The present study conducted a focused analysis of potential candidate or susceptibility genes for common genetic generalized epilepsy syndromes using multi-gene panel testing with next-generation sequencing. This study included patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We identified pathogenic variants according to the American College of Medical Genetics and Genomics guidelines and identified susceptibility variants using case-control association analyses and family analyses for familial cases. A total of 57 patients were enrolled, including 51 sporadic cases and 6 familial cases. Twenty-two pathogenic and likely pathogenic variants of 16 different genes were identified. CACNA1H was the most frequently observed single gene. Variants of voltage-gated Ca2+ channel genes, including CACNA1A, CACNA1G, and CACNA1H were observed in 32% of variants (n = 7/22). Analyses to identify susceptibility variants using case-control association analysis indicated that KCNMA1 c.400G>C was associated with common genetic generalized epilepsy syndromes. Only 1 family (family A) exhibited a candidate pathogenic variant p.(Arg788His) on CACNA1H, as determined via family analyses. This study identified candidate genetic variants in about a quarter of patients (n = 16/57) and an average of 2.8 variants was identified in each patient. The results reinforced the polygenic disorder with very high locus and allelic heterogeneity of common GGE syndromes. Further, voltage-gated Ca2+ channels are suggested as important contributors to common genetic generalized epilepsy syndromes. This study extends our comprehensive understanding of common genetic generalized epilepsy syndromes.
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影响因子：
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通讯作者：
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