RASores

RASopathies are a group of genetically-driven developmental disorders characterized by constitutive activation of the RAS/MAPK signaling pathway due to mutations in a pathway protein or its regulator.

Patients with these syndromes (e.g., Noonan, Costello, Cardio-Facio-Cutaneous, CBL syndromes) share common phenotypic features: growth retardation, cardiopathy, dysmorphia, intellectual disability, skin and lymphatic abnormalities, hemostasis disorders, and malignancies such as juvenile myelomonocytic leukemia (JMML). However, there is high inter-individual variability, which remains poorly understood.

The implementation of a unified data warehouse (RASORES) linked to a virtual biobank will enable the identification of new genotype–phenotype correlations in patients with RASopathies through a cohort study on the natural history of the disease, neuropsychological and social consequences, and preclinical pathophysiological investigations.

The data warehouse, hosted by France Cohortes, will be cloned as a sub-registry for RASopathies within the ILIAD EDS (the European registry of the ERN ITHACA dedicated to developmental and neurodevelopmental disorders) and will be interoperable with other European databases.

By enabling new genotype–phenotype correlations, RASores will improve patient management (diagnosis, monitoring, and information for patients and families) and support personalized medicine approaches for drug development.

RASores addresses two major challenges in RASopathies (prevalence 1:2,000):

1. Clinical: delineating rare and late-onset complications, which require systematic cohort approaches to be reliably assessed, and evaluating their psychosocial impact.
2. Fundamental/translational: through the virtual biobank linked to the EDS, the project seeks to elucidate pathogenic mechanisms underlying cardinal features of RASopathies—a longstanding priority of the project partners.

RASopathies are potential candidates for therapies targeting RAS/MAPK signaling, yet no targeted therapy currently exists.

• Alain VERLOES – Head of Clinical Genetics Department, APHP – Université de Paris Cité, Robert DEBRE University Hospital, Paris
• Hélène CAVÉ – Head of Molecular Genetics Department, APHP – Université de Paris Cité, Robert DEBRE University Hospital, Paris

Claudine CHARLES, PhD – Project Manager

claudine.charles@aphp.fr 

This data management work provided by France Cohortes benefits from government support administered by the French National Research Agency (ANR) under the France 2030 program, reference ANR-21-PMRB-0010.

Partners