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.

Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy

Project Coordinator

Radboud university medical center
The Netherlands


Giuseppe Testa Istituto Europeo di Oncologia Milan, Italy
James Ellis SickKids Hospital Toronto, Canada
Gaia Novarino Institute of science and technology Klosterneuburg, Austria
Giacomo Cavalli Institut de Génétique Humaine (UMR9002) Montpellier, France
Frank Kooy University of Antwerp Edegem, Belgium

Neurodevelopmental disorders (NDDs) represent a large and heterogeneous group of disorders. Individual types of NDDs, with a known genetic etiology are typically rare, owing to the very high number of individual genes that are causative for such conditions. The most mutated genes are involved in synaptic processes and in transcription regulation through modulation of chromatin structure (“epigenetic mechanisms”). In this proposal we study five distinct NDDs: Kabuki, Kleefstra, Gabriele-de Vries, Helsmoortel-Van der Aa, and a syndromic type of ASD, caused respectively by mutations in KMT2D, EHMT1, YY1, ADNP and CHD8, which are involved in transcription and chromatin structure regulation. These syndromes share overlapping clinical features, are connected each other by the molecular role of the causative genes, which are further connected by molecular partners. We hypothesize that mutations in these five genes give rise to unique as well as common downstream effects in gene transcription and translation. Therefore, the IMPACT collaborative project aims to reveal common molecular and cellular signatures of chromatinopathy gene disruptions. The common converging disease mechanisms are attractive targets for therapeutic intervention. Such converging mechanisms of disease offer an attractive target for the development of knowledge-based therapeutic interventions across individual NDDs that can potentially be useful for designing interventions suitable for multiple related rare neurodevelopmental disorders.

E-Rare 2012 - Created by Toussaint Biger