Next-Generation Sequencing Technologies and Neurogenetic Diseases

Abstract

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.

Opportunities and challenges of 5G network technology toward precision medicine

“…14 Several studies reported that targeted NGS enabled the detection of disease-causing mutations for the clinical diagnosis of Mendelian diseases, which include hereditary metabolic disease, respiratory disease, cardiovascular disease, cancer, hereditary kidney disease, and neurogenetic diseases. [15][16][17] Metabolic syndrome (e.g., high blood pressure, high triglyceride, and high glucose) and metabolic diseases (e.g., type 2 diabetes mellitus, atherosclerosis, non-alcoholic fatty liver disease, and obesity) are alarming health burdens globally as their etiologies are not completely elucidated, making it a challenge for enabling effective treatment and prevention. 18 The utility of NGS involves the storage of vast amounts of complex and heterogeneous data that requires high speed for generating and moving data around.…”

“…The advancement of NGS has driven the discovery of novel disease targets, as well as therapeutic identification, prenatal testing, or even disease diagnosis 14 . Several studies reported that targeted NGS enabled the detection of disease‐causing mutations for the clinical diagnosis of Mendelian diseases, which include hereditary metabolic disease, respiratory disease, cardiovascular disease, cancer, hereditary kidney disease, and neurogenetic diseases 15–17 . Metabolic syndrome (e.g., high blood pressure, high triglyceride, and high glucose) and metabolic diseases (e.g., type 2 diabetes mellitus, atherosclerosis, non‐alcoholic fatty liver disease, and obesity) are alarming health burdens globally as their etiologies are not completely elucidated, making it a challenge for enabling effective treatment and prevention 18 .…”

Novel variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability in Iranian consanguineous families

“… 3 Therefore, NGS has increased the number of causative genes liked to ID facilitating in the diagnosis of the patients. 4 …”

Whole exome screening of neurodevelopmental regression disorders in a cohort of Egyptian patients

“…WES is an appropriate method for finding new mutations and thousands of variants, including missense variants, protein-truncating variants, and large structural variants (SVs); however, whole genome sequencing (WGS) is suitable for exploring the roles of specific and de novo genes in neurodegenerative disorders. A combination of clinical and molecular analysis has become a more effective diagnosis approach [ 12 ]. We aimed to highlight genes causing developmental regression and neurodegenerative disorders in Egypt using NGS-based analyses, including interpretations of different variants and mutations.…”