Next Generation Sequencing Methods for Diagnosis of Epilepsy Syndromes.
Next Generation Sequencing Methods for Diagnosis of Epilepsy Syndromes.
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DOI：
10.3389/fgene.2018.00020
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发表时间：
2018
影响因子：
3.7
通讯作者：
Griffiths LR
中科院分区：
文献类型：
--
作者：
Dunn P;Albury CL;Maksemous N;Benton MC;Sutherland HG;Smith RA;Haupt LM;Griffiths LR
癫痫是一种神经系统疾病，其特征是癫痫发作倾向增加。尽管这个定义表明癫痫是一种单一疾病，但它包含一组具有不同病因和结果的疾病。癫痫综合征的遗传基础已经被假设了几十年，并且确定了特定基因的几种突变，这增加了我们对遗传对癫痫影响的理解。 70-80% 的癫痫病例被确定为遗传原因，目前已确定数百个与癫痫综合征相关的基因，可以使用下一代测序 (NGS) 技术进行分析，例如靶向基因组、全外显子组测序 (WES) 和全基因组测序 (WGS)。为了有效使用这些方法，诊断实验室和临床医生需要相关工作流程的信息，包括分析和测序深度，以了解这些基因测序技术的具体临床应用和诊断能力。由于癫痫是一种复杂的疾病，每种技术的差异都会影响诊断以及准确检测该疾病的遗传病因的能力。此外，对于诊断测试，一个重要参数是每种技术的成本效益和具体诊断结果。在这里，我们回顾这些常用的 NGS 技术，以确定它们是否适合应用于癫痫基因诊断检测。
Epilepsy is a neurological disorder characterized by an increased predisposition for seizures. Although this definition suggests that it is a single disorder, epilepsy encompasses a group of disorders with diverse aetiologies and outcomes. A genetic basis for epilepsy syndromes has been postulated for several decades, with several mutations in specific genes identified that have increased our understanding of the genetic influence on epilepsies. With 70-80% of epilepsy cases identified to have a genetic cause, there are now hundreds of genes identified to be associated with epilepsy syndromes which can be analyzed using next generation sequencing (NGS) techniques such as targeted gene panels, whole exome sequencing (WES) and whole genome sequencing (WGS). For effective use of these methodologies, diagnostic laboratories and clinicians require information on the relevant workflows including analysis and sequencing depth to understand the specific clinical application and diagnostic capabilities of these gene sequencing techniques. As epilepsy is a complex disorder, the differences associated with each technique influence the ability to form a diagnosis along with an accurate detection of the genetic etiology of the disorder. In addition, for diagnostic testing, an important parameter is the cost-effectiveness and the specific diagnostic outcome of each technique. Here, we review these commonly used NGS techniques to determine their suitability for application to epilepsy genetic diagnostic testing.