Dissecting the pathomolecular mechanisms of Prr12 gene inactivation leading to neurodevelopmental and eye abnormalities.

This project has been funded thanks to the Joint Call Fondazione Cariplo and Fondazione Telethon 2021

Neurodevelopmental disorders (NDDs) are a class of pathologies affecting brain development and function, and represent a major social problem in all countries. NDDs include a large variety of rare diseases with heterogeneous etiology and share deficits leading to impaired cognitive abilities, communication, adaptive behavior, and psychomotor skills. These pathological conditions are often associated with a variety of clinical problems including developmental delay, craniofacial defects and ocular disorders and their heterogeneity poses many limitations to an effective therapeutic approach. Nevertheless, recent technological advances in the ability to discover new genes and to associate their malfunctioning to specific diseases has accelerated the identification of the genetic causes of several neurodevelopmental syndromes. A newly discovered cause for neurodevelopmental disorders is the partial inactivation (haploinsufficiency) of PRR12, a gene whose function has not been characterized yet. The goal of our project is to understand the role of PRR12 in neuronal cells, thus allowing the identification of the molecular mechanisms affected in the pathology. Furthermore, our investigation on the interaction between PRR12 and SOX2, a gene whose haploinsufficiency causes another neurodevelopmental syndrome, will highlight similarities and differences in their mechanisms of action. The obtained results will provide precious information for designing new future therapeutic interventions.