Funding transnational collaborative research through joint transnational calls is one of the major objectives of E-Rare. This is the most important and effective joint activity to enhance the cooperation between European scientists working on rare diseases and thus reducing the fragmentation of research in this field. E-Rare launches calls on a yearly basis. The topic and eligibility criteria are specified every year and therefore may vary from one call to the other.

The Netherlands
European network on noonan syndrome and related disorders

Project Coordinator

Instituto Superiore di Sanita Ematologia, Oncologia e Medicina Molecolare


Hélène Cavé CHU Robert Debré Université Denis Diderot Paris VII Genetics Paris, France
Martin Zenker University Hospital of Erlangen University of Erlangen-Nuremberg Erlangen, Germany
Patrick Raynal INSERM U563 Centre de Physiopathologie de Toulouse-Purpan Toulouse, France
Reza AHMADIAN Heinrich Heine Medical Center Biochemistry and Molecular Biology II (IMBM) Düsseldorf, Germany
Ype Elgersma Erasmus University Center (EMC) Neuroscience Rotterdam, The Netherlands

Publications of the NSEuroNet project

Major results of the project

RASopathies constitute an emerging family of disorders affecting development and growth. This group of diseases includes Noonan syndrome, cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, and an increasing number of other clinically related conditions sharing dysregulation of RAS signaling as common pathogenetic mechanism. Clinical manifestations of RASopathies include postnatal reduced growth, a wide spectrum of cardiac defects, facial dysmorphism, ectodermal and skeletal anomalies, variable cognitive deficits, and increased risk for certain hematologic malignancies and other pediatric cancers. Most of these conditions are genetically heterogeneous, and the underlying genetic cause has not been identified yet for a still large fraction of cases. Understanding the molecular bases of RASopathies is a requisite to diagnose and treat these disorders effectively as well as for a more efficient patient management and risk assessment.
Major goals of this project were to understand the molecular events implicated in disease pathogenesis, assess the prevalence and diversity of RASopathy gene mutations and their associated phenotypic diversity, delineate clinically relevant genotype-phenotype correlations, and provide innovative tools for early diagnosis and the development of therapeutic intervention. Major findings of this Consortium follow.
A gene candidacy approach was used to discover three novel RASopathy genes (NRAS, CBL and RRAS). Biochemical and functional characterization of disease-causing mutations has provided novel insights on pathogenesis. Specifically, these studies have delineated the consequences of Noonan syndrome and LEOPARD syndrome causative PTPN11 mutations on SHP2 function and intracellular signaling. Research has also been directed to dissect the differential structural and functional impact of disease-causing KRAS and HRAS mutations. Finally, the partners of this Consortium have contributed significantly to a number of multicentric, clinically oriented studies, making available new data that will help clinicians towards a timely diagnosis and efficient patient management, as well as to research directed to the development of new in vitro tools for future translational research studies.

E-Rare 2012 - Created by Toussaint Biger