[MS5] Morning Seminar 5: NGS

[MS5-3A-1] Application of high-throughput sequencing in child neurology

^○Ganeshwaran Hitoshi MOCHIDA^{1, 2, 3} (1.Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA, USA, 2.Pediatric Neurology Unit, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA, 3.Department of Pediatrics, Harvard Medical School, Boston, MA, USA)

Genetic etiology accounts for many neurological disorders of pediatric onset and therefore genetic testing is an important part of child neurology practice. High-throughput sequencing, particularly whole-exome and whole-genome sequencing, has become more widely available, uncovered diagnoses in individuals who were previously undiagnosed and contributed to the identification of many new disease genes. However, there are challenges in applying high-throughput sequencing to clinical practice. These include: 1) limited access to high-throughput sequencing in many parts of the world, 2) variable sequencing and analysis methodologies and reporting practices, 3) underrepresentation of many populations in public databases of genetic variants, 4) highly heterogeneous nature of many pediatric neurological disorders, 5) numerous unidentified causative genes in pediatric neurological disorders, and 6) difficulty in proving pathogenicity of novel variants. This presentation aims to describe what practicing pediatric neurologists should know about applying high-throughput sequencing to their clinical practice. Examples of using high-throughput sequencing to identify novel disease genes in research will be presented and future directions in clinical and research applications of high-throughput sequencing will be discussed.