Department of Medical Genetics and Department of Paedaitric Clinical Epileptology, Member of the ERN EpiCARE, University Hospitals of Lyon (HCL), Lyon, France; University Claude Bernard Lyon 1, Lyon, France.
Department of Epileptology, University Hospital Bonn, Member of the ERN EpiCARE, Bonn, Germany.
Eur J Med Genet. 2022 Sep;65(9):104570. doi: 10.1016/j.ejmg.2022.104570. Epub 2022 Jul 16.
In past decades, the identification of genes involved in epileptic disorders has grown exponentially. The pace of gene identification in epileptic disorders began to accelerate in the late 2000s, driven by new technologies such as molecular cytogenetics and next-generation sequencing (NGS). These technologies have also been applied to genetic diagnostics, with different configurations, such as gene panels, whole-exome sequencing and whole-genome sequencing. The clinician must be aware that any technology has its limitations and complementary techniques must still be used to establish a diagnosis for specific diseases. In addition, increasing the amount of genetic information available in a larger patient sample also increases the need for rigorous interpretation steps, when taking into account the clinical, electroclinical, and when available, functional data. Local, multidisciplinary discussions have proven valuable in difficult diagnostic situations, especially in cases where precision medicine is being considered. They also serve to improve genetic counseling in complex situations. In this article, we will briefly review the genetic basis of rare and common epilepsies, the current strategies used for molecular diagnosis, including their limitations, and some pitfalls for data interpretation, in the context of etiological diagnosis and genetic counseling.
在过去的几十年中，与癫痫相关的基因的鉴定呈指数级增长。在 21 世纪后期，随着分子细胞遗传学和下一代测序（NGS）等新技术的出现，癫痫症的基因鉴定速度开始加快。这些技术也已应用于遗传诊断，具有不同的配置，如基因面板、外显子组测序和全基因组测序。临床医生必须意识到任何技术都有其局限性，仍必须使用互补技术来为特定疾病建立诊断。此外，随着更大患者样本中遗传信息量的增加，在考虑临床、电临床和可用的功能数据时，还需要更严格的解释步骤。在困难的诊断情况下，当地的多学科讨论已被证明是有价值的，特别是在考虑精准医学的情况下。它们还有助于在复杂情况下改善遗传咨询。在本文中，我们将简要回顾罕见和常见癫痫的遗传基础、当前用于分子诊断的策略，包括其局限性，以及在病因诊断和遗传咨询背景下数据解释的一些陷阱。
