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
Congenital neutropenia with ELA-2 mutations (ELA2-CN): Identification of (epi)genetic co-factors and molecular pathways underlying clinical heterogeneity

Project Coordinator

Hannover Medical School Molecular Hematopoiesis


Cornelia Zeidler Hannover Medical School Molecular Hematopoiesis Hannover, Germany
Deniz Yilmaz Karapinar Ege University Faculty of Medicine Childrens Hospital Department of Pediatric Hematology Bomova-Izmir, Turkey
Hannah Tamary Schneider Children's Medical Center of Israel Pediatric Hematology Petah Tikva, Israel
Ivo Touw Erasmus University Medical Center Hematology Office H EE13-30c Rotterdam, The Netherlands
Paul J. Coffer University Medical Center Molecular Immunology Lab Department of Immunology & Pediatrics Ultrech, The Netherlands

Congenital neutropenia patients with ELA2 mutations (ELA2-CN) and cyclic neutropenia patients harbouring ELA2 mutations (ELA2-CyN) represent approx. 60% of inherited neutropenia patients in Europe and North America. Other genetic defects causing CN like HAX1-, G6PC3-mutations have been identified in minor cohorts of consanguineous families in Europe only. Although both, the phenotype of CN and CyN are related to identical ELA2-mutations, the clinical course differs significantly: ELA2-CN patients have a high risk for secondary leukemias, require higher G-CSF doses and develop G-CSF receptor mutations, whereas ELA2-CyN respond to lower G-CSF doses without malignant transformation showing the typical cycling of neutrophil counts throughout their life. It is still unknown how ELA2 mutations contribute to these different clinical phenotypes. We hypothesize the existence of modifying molecular defects and mutator genes in patients with ELA2 mutations discriminating between the two major phenotypes (CN and CyN). Within the applied network we will identify families with patients suffering from ELA2-CN or ELA2-CyN to compare the molecular findings with healthy family members by SNP technology. In addition, we will share the material to investigate the pathomechanisms of specific mutations regarding G-CSF receptor signalling, transcription factor dysfunctions, chromatin remodelling and mouse models for leukemogenesis.

E-Rare 2012 - Created by Toussaint Biger