Joint Transnational Call 2015 (JTC2015)


RASopathies constitute a family of rare diseases affecting development and growth. These disorders include Noonan syndrome and an increasing number of clinically related conditions sharing dysregulation of RAS signaling as common pathogenetic mechanism. Major features include reduced growth, congenital heart disease, hypertrophic cardiomyopathy, cognitive deficits, facial dysmorphism, skeletal and hematologic anomalies, and variable predisposition to certain malignancies. Most of these disorders are genetically heterogeneous, and the partners of this Consortium have significantly contributed to our understanding of the molecular causes underlying these diseases, providing new tools for diagnosis and patient management. There are fundamental questions about pathogenesis, however, that still remain unanswered. Moreover, a large fraction of RASopathy cases does not have diagnosis or still remains unexplained molecularly. Goals of the proposed research are to explore further the molecular bases of these disorders by identifying novel disease genes and understand pathogenesis using complementary in silico, in vitro and in vivo models. Work will be directed to provide accurate molecular epidemiology data and delineate genotype-phenotype correlations that will help clinicians towards a timely diagnosis and a more effective patient management and risk assessment. Finally, we plan to validate compounds to restore proper RAS signaling as a new approach for the development of therapeutic interventions to ameliorate evolutive complications of these diseases.

  • Tartaglia, Marco (Coordinator)
    Institute Superiore di Sanità [ITALY]
  • Zenker, Martin
    Otto-von-Guericke University Magdeburg [GERMANY]
  • Ahmadian, Reza
    Heinrich-Heine University [GERMANY]
  • Den Hertog, Jeroen
    Koninklijke Nederlandse Academie van Wetenschappen  [NETHERLANDS]
  • Cavé, Helene
    CHU Robert Debré [FRANCE]
  • Yart, Armelle