Whole Exome Sequencing in neurodevelopmental disorders and development of innovative disease-relevant cellular models.

Neurodevelopmental disorders (ND) are highly heterogeneous conditions, including autism spectrum disorders (ASD) and intellectual disability (ID), characterized by extensive clinical and molecular overlap. Our group has started in 2015 a research project named NeuroWes, whose aim is performing TRIO-based whole exome sequencing (WES) in families with ID/ASD in collaboration with the Autism Sequencing Consortium (ASC, Icahn School of Medicine at Mount Sinai, New York, USA), a multicentric international initiative aimed at identifying the genetic bases of these neurodevelopmental disorders. At present our group have collected, sequenced and analysed by WES about 300 families with ID/ASD (~ 1000 samples), allowing a 38% diagnostic rate in the whole survey of neurodevelopmental disorders, and 27% considering ASD only.

The development of prognostic cell models that mimic brain physiology or specific neurological diseases is essential to study the pathogenic mechanisms underlying these conditions and to identify effective therapeutic approaches for patients. Coping with this increased need, we are collecting stem cells isolated from deciduous teeth of children affected by ND and from healthy subjects. These stem cells can be differentiated in vitro into mesenchymal or neuronal cells and exploited as disease-relevant cellular models.