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.

Inherited inhibition of inborn immunity – an integrated molecular genetic approach to discover novel human gene defects

Project Coordinator

Hannover Medical School Pediatric Hematology/Oncology


Jean Donadieu Hôpital Trousseau AP HP Registre Français des Neutropénies Congénitales Service d'Hémato-Oncologie Pédiatrique Paris, France
Josef Penninger Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Science Vienna, Austria
Necil Kutukculer Ege University School of Medicine Pediatrics, Division of Pediatric Immunology Izmir, Turkey
Philippe Herbomel Institut Pasteur and CNRS Developmental Biology Paris, France

Publications of the NEUTRO-NET project

Major results of the project

Neutrophil granulocytes are part of the inborn immune defense and represent the most prevalent type of white blood cells. They are indispensable for the defense against pathogens. Severe congenital neutropenia (SCN) is a primary immunodeficiency syndrome characterized by reduced neutrophil cell numbers and increased susceptibility for severe bacterial and fungal infections leading to recurrent severe life threatening infections. SCN comprises a heterogeneous group of monogenetic disorders resulting in neutropenia and various further symptoms. Genetic investigations lead to the discovery of several genetic mutations associated with SCN; however in approximately 40-50 % of patients the underlying mutation is unknown.
The implementation of clinical registries has greatly facilitated the scientific investigations of rare diseases and the immune system. A number of national and international registries for patients with PID have been established, however, patients from areas with high prevalence of consanguinity were still underrepresented.
The aim of the project was to provide novel insights into the pathophysiology of inborn errors of neutrophil function and a more comprehensive understanding of neutrophil biology. The partners proposed to build on an established network of international clinical collaborations, to employ state-of-the art genetic screening systems and to make use of powerful genetic model organisms to analyse the newly identified human genetic defects. Altogether, the NEUTRO-NET consortium aimed to efficiently spread the basis and applied knowledge on mechanisms and genes involved in inborn myeloid immunodeficiency syndromes and thereby to contribute to the benefit of affected families and patient care.

The collaboration of the NEUTRO-NET partners yielded in various important achievements in the field of rare inborn genetic defects of the myeloid cells of immune system and lead to various publications in high ranking scientific journals.
The consolidation of the network of international clinical collaborations and notably the connections of the French and Turkish partners to Northern African and further countries with high level of consanguinity lead to the enlargement of the existing national and international clinical patients registries and provided patient samples from consanguineous families. These registries built the basis for our screening of patients with rare genetic. The emphasis laid the systematic analysis of patients at the different partner sites. The partners systematically characterized the clinical phenotype of a multitude of patients suffering from defined immunological deficiencies. Furthermore, they recruited within the existing networks informative families for genetic analysis to identify novel genetic defects. During the funding period, several genetic defects have been identified and described. To this purpose the patients have been clinically examined in detail. To determine the relevance of the identified genetic variations, the consortium compared the DNA sequence of the patients with DNA samples of the corresponding ethnic groups. To assess the function of the affected genes, functional studies have been performed in cultured cells (‘in vitro’) and in model organisms (‘in vivo’) and were still ongoing after the end of the funding period. During the course of this grant, a breakthrough in genetics was made by the discovery of haploid mammalian embryonic stem cells by the Austrian partner. On this basis, they developed a novel tool for high throughput genetics which is now used in several further projects. The work is still ongoing. The E-RARE funding built the basis for new collaborations with further partners and enabled successful grant applications. Altogether, our results build a basis for the development of diagnostic approaches and future therapeutic strategies.

E-Rare 2012 - Created by Toussaint Biger