Sun Hui, Shen Xiao-Rong, Fang Zi-Bing, Jiang Zong-Zhi, Wei Xiao-Jing, Wang Zi-Yi, Yu Xue-Fan
Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun 130021, China.
Life (Basel). 2021 Apr 19;11(4):361. doi: 10.3390/life11040361.
Next-generation sequencing (NGS) technology has led to great advances in understanding the causes of Mendelian and complex neurological diseases. Owing to the complexity of genetic diseases, the genetic factors contributing to many rare and common neurological diseases remain poorly understood. Selecting the correct genetic test based on cost-effectiveness, coverage area, and sequencing range can improve diagnosis, treatments, and prevention. Whole-exome sequencing and whole-genome sequencing are suitable methods for finding new mutations, and gene panels are suitable for exploring the roles of specific genes in neurogenetic diseases. Here, we provide an overview of the classifications, applications, advantages, and limitations of NGS in research on neurological diseases. We further provide examples of NGS-based explorations and insights of the genetic causes of neurogenetic diseases, including Charcot-Marie-Tooth disease, spinocerebellar ataxias, epilepsy, and multiple sclerosis. In addition, we focus on issues related to NGS-based analyses, including interpretations of variants of uncertain significance, de novo mutations, congenital genetic diseases with complex phenotypes, and single-molecule real-time approaches.
下一代测序（NGS）技术在理解孟德尔和复杂神经系统疾病的病因方面取得了巨大进展。由于遗传疾病的复杂性，导致许多罕见和常见神经系统疾病的遗传因素仍知之甚少。基于成本效益、覆盖范围和测序范围选择正确的基因检测方法可以改善诊断、治疗和预防。全外显子组测序和全基因组测序是发现新突变的合适方法，基因检测板适用于探索特定基因在神经遗传疾病中的作用。在此，我们概述了NGS在神经系统疾病研究中的分类、应用、优点和局限性。我们还进一步提供了基于NGS探索神经遗传疾病遗传病因的实例和见解，包括夏科-马里-图斯病、脊髓小脑共济失调、癫痫和多发性硬化症。此外，我们关注基于NGS分析的相关问题，包括意义未明变异、新发突变、具有复杂表型的先天性遗传疾病以及单分子实时方法的解读。
