Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy
Next-generation sequencing improves treatment efficacy and reduces hospitalization in children with drug-resistant epilepsy
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下一代测序可提高耐药性癫痫儿童的治疗效果并减少住院率
DOI：
10.1111/cns.12869
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发表时间：
2019-01-01
影响因子：
5.5
通讯作者：
Yin, Fei
中科院分区：
文献类型：
--
作者：
Peng, Jing;Pang, Nan;Yin, Fei
本研究的目的有三个：（i）确定已知基因对广谱儿科耐药癫痫（DRE）病因的贡献，（ii）比较不同下一代测序（NGS）方法之间的诊断率和成本，特别是（iii）评估NGS方法如何通过提高诊断和治疗效率使患者受益。方法对273例无明显后天病因的DRE患儿进行回顾性分析。74例患者进行了全外显子组测序（WES），141例患者进行了癫痫相关基因面板检测，另外58例患者进行了临床WES基因面板检测。我们通过定期电话随访和门诊访视获得这些患者的癫痫发作和住院频率。结果86例患者（31.5%）获得基因诊断，涉及33个基因的93个可能致病的突变。本研究中，癫痫相关基因组、临床WES基因组和WES的检出率分别为32.6%（46/141）、44.8%（26/58）和17.3%（13/74）。34例患者根据突变基因进行纠正治疗后，52.9%（18/34）的患者无癫痫发作，38.2%（13/34）的患者癫痫发作减少。最后，遗传结果阳性或阴性的患者的住院事件（次数/半年）比以前显著减少（遗传结果阳性组0.58 +/- 1.14 vs 0.10 +/- 0.26;遗传结果阴性组0.72 +/- 1.65 vs 0.12 +/- 0.33）。结论这些结果进一步证明NGS方法是建立明确诊断的有力工具。此外，这项研究表明NGS如何提高DRE儿童的治疗效果并减少住院治疗。
Background The purposes of this study were three-fold: (i) to determine the contribution of known genes to the causation of a broad-spectrum of pediatric drug-resistant epilepsy (DRE), (ii) to compare the diagnostic yield and cost among different next-generation sequencing (NGS) approaches, and especially (iii) to assess how NGS approaches can benefit patients by improving diagnosis and treatment efficiency. Methods This study enrolled 273 pediatric DRE patients with no obvious acquired etiology. Seventy-four patients underwent whole-exome sequencing (WES), 141 patients had epilepsy-related gene panel testing, and another 58 patients had clinical WES gene panel testing. We obtained these patients' seizure and hospitalization frequency by periodic follow-up phone calls and outpatient visits. Results Genetic diagnosis was achieved in 86 patients (31.5%) and involved 93 likely disease-causing mutations in 33 genes. In this study, the detection rates of the epilepsy-related gene panel, the clinical WES gene panel, and WES were 32.6% (46/141), 44.8% (26/58), and 17.3% (13/74), respectively. Moreover, 34 patients accepted corrective therapy according to their mutant genes, after which 52.9% (18/34) became seizure-free and 38.2% (13/34) achieved seizure reduction. In the end, patients with either positive or negative genetic results had significantly fewer hospitalization incidents (times/half year) than before (positive genetic results group 0.58 +/- 1.14 vs 0.10 +/- 0.26; negative genetic results group 0.72 +/- 1.65 vs 0.12 +/- 0.33). Conclusions These results offer further proof that NGS approaches represent powerful tools for establishing a definitive diagnosis. Moreover, this study indicated how NGS can improve treatment efficacy and reduce hospitalization in children with DRE.