Over the past 10 years, the increasingly important role played by next-generation sequencing panels in the genetic diagnosis of epilepsy has led to a growing list of gene variants and a plethora of new scientific data. To date, however, there is still no consensus on what constitutes the “ideal panel design,” or on the most rational criteria for selecting the best candidates for gene-panel analysis, even though both might optimize the cost-benefit ratio and the diagnostic efficiency of customized gene panels. Even though more and more laboratories are adopting whole-exome sequencing as a first-tier diagnostic approach, interpreting, “in silico,” a set of epilepsy-related genes remains difficult. In the light of these considerations, we performed a systematic review of the targeted gene panels for epilepsy already reported in the available scientific literature, with a view to identifying the best criteria for selecting patients for gene-panel analysis, and the best way to design an “ideal,” gold-standard panel that includes all genes with an established role in epilepsy pathogenesis, as well as those that might help to guide decisions regarding specific medical interventions and treatments. Our analyses suggest that the usefulness and diagnostic power of customized gene panels for epilepsy may be greatest when these panels are confined to rationally selected, relatively small, pools of genes, and applied in more carefully selected epilepsy patients (those with complex forms of epilepsy). A panel containing 64 genes, which includes the 45 genes harboring a significant number of pathogenic variants identified in previous literature, the 32 clinically actionable genes, and the 21 ILAE (International League Against Epilepsy) recommended genes, may represent an “ideal” core set likely able to provide the highest diagnostic efficiency and cost-effectiveness and facilitate gene prioritization when testing patients with whole-exome/whole-genome sequencing.

中文翻译：

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癫痫病中定制的多基因面板：最好的东西装在小包装中。

在过去的十年中，下一代测序专家组在癫痫病的基因诊断中扮演着越来越重要的角色，从而导致越来越多的基因变体列表和大量新的科学数据。然而，迄今为止，关于“理想的面板设计”的构成或选择基因面板分析的最佳候选者的最合理标准仍未达成共识，即使两者都可以优化成本效益比和诊断方法。定制基因板的效率。尽管越来越多的实验室采用全基因组测序作为第一级诊断方法，但在“计算机模拟”中解释，与癫痫相关的一组基因仍然很困难。鉴于这些考虑，我们对现有的科学文献中已报道的癫痫的靶向基因组进行了系统的综述，以期确定选择患者进行基因组分析的最佳标准，以及设计“理想的”金-方法的最佳方法。标准面板，其中包括在癫痫发病机制中已确立作用的所有基因，以及可能有助于指导有关特定医学干预和治疗的决策的基因。我们的分析表明，当定制的基因组仅限于合理选择的，相对较小的基因库，并应用于更仔细选择的癫痫患者（患有复杂形式的癫痫患者）中时，定制的基因组对癫痫的有用性和诊断力可能最大。 。包含64个基因的面板，