Translational and clinical research applications of exome sequencing to neurodevelopmental disorders of childhood

Neurodevelopmental disabilities (NDDs) are a group of chronic clinically distinct disorders sharing a documented disturbance, quantitative, qualitative, or both, in developmental progress in one or more developmental domains compared with established norms. These domains are not mutually independent or exclusive and include: (1) motor (gross or fine), (2) speech and language, (3) cognition, (4) personal-social, and (5) activities of daily living (Shevell et al., 2008). Whole Exome Sequencing (WES) has provided a huge contribution to the discovery of disease-causing variants for rare diseases, especially neurodevelopmental disorders. Furthemore, the use of WES in clinical practice has improved the diagnostic rate in several rare genetic conditions, including neurodevelopmental disorders, which previously remained unexplained (Xue et al., 2014). This has led to a relevant improvement in patient management in selected disorders. Indeed, the better understanding of the pathophysiology underlying a specific condition has helped clinicians in developing a disease-specific approach in patient care. Furthermore, the identification of several new possible therapeutic targets has promoted the development of new therapeutic strategies or specific drugs. In this study, we investigated the use of exome sequencing in three different genomic research approaches: genotype-phenotype correlations; pathophysiological mechanisms; gene discovery. Our findings show that NGS techniques play a pivotal role in the NDDs research.