[MS5] Morning Seminar 5: NGS

[MS5-3A-3] Clinical Application of Whole Exome Sequencing in Patients with Uncertain Neurological Disorders

^○Murim Choi^{1, 2} (1.Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea,, 2.Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, Korea)

Inherent complexity of brain developmental processes inevitably generates patients with neurological defects of varying degrees that frequently challenge conventional diagnostic criteria. Therefore, accurate diagnosis of the patients with unconventional or complicated pediatric neurological defects demands well-coordinated combination of robust genetic analytic ability and delicate clinical evaluation. Using a trio-based whole exome sequencing approach, we analyzed 293 patients with a broad spectrum of neurological disorders without any pathogenic variants revealed by the conventional methods. Overall, we identified disease-causing variants in 53% of the probands and 47% of them were previously reported as pathogenic. We also discovered 55 potentially pathogenic variants that require further functional assessments (18.4% of total analyzed). Furthermore, we introduce a few clinical vignettes that well illustrate potential diagnostic pitfalls that one could have encountered without this approach. Our results highlight the heterogeneity of clinical and genetic profiles of pediatric neurology patients and propose utility of whole exome sequencing for improved patient care and discovery of novel pathophysiology mechanisms.