Advances in genome sequencing technologies have unlocked new possibilities in identifying disease-associated and causative genetic markers, which may in turn enhance disease diagnosis and improve prognostication and management strategies. With the capability of examining genetic variations ranging from single-nucleotide mutations to large structural variants, whole-genome sequencing (WGS) is an increasingly adopted approach to dissect the complex genetic architecture of neurologic diseases. There is emerging evidence for different structural variants and their roles in major neurologic and neurodevelopmental diseases. This review first describes different structural variants and their implicated roles in major neurologic and neurodevelopmental diseases, and then discusses the clinical relevance of WGS applications in neurology. Notably, WGS-based detection of structural variants has shown promising potential in enhancing diagnostic power of genetic tests in clinical settings. Ongoing WGS-based research in structural variations and quantifying mutational constraints can also yield clinical benefits by improving variant interpretation and disease diagnosis, while supporting biomarker discovery and therapeutic development. As a result, wider integration of WGS technologies into health care will likely increase diagnostic yields in difficult-to-diagnose conditions and define potential therapeutic targets or intervention points for genome-editing strategies.
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.