European network on Noonan syndrome and related disorders (NSEuroNet)

RASopathies constitute the most common family of non-chromosomal disorders affecting development. This group of rare diseases includes an increasing number of conditions characterized by reduced growth, heart defects, cognitive deficits, dysmorphisms and variable predisposition to malignancies. RASopathies share upregulated RAS-MAPK and/or PI3K-AKT-mTOR signaling as pathogenetic mechanism. The planned work, which is the natural follow-up of a previously funded E-Rare project, is directed to resolve the functional consequences of a large panel of uncharacterized mutations, generate in vitro and in vivo gene/mutation-specific models, characterize novel circuits modulating RAS signaling, explore the pathophysiology of key complications of these diseases, and identify novel disease genes. Work will also be directed to populate a dedicated database that will be used for clinically oriented studies to help clinicians towards a timely diagnosis and a more effective patient care.