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.

Genetics, Pathophysiology, and Therapy of Hereditary Angioedema Type III

Project Coordinator

University of Bonn, Life & Brain Center Department of Genomics


Christian Drouet University Joseph Fourier Grenoble National Centre for Angioedema Grenoble, France
Hans Christian Hennies Cologne Center for Genomic Division of Dermatogenetics Köln, Germany
Konrad Bork University of Mainz Department of Dermatology Mainz, Germany
Roberto Colombo IRCCS Don Carlo Gnocchi Foundation Laboatory of Molecular Medicine and Biotechnologies Milano, Italy
Thomas Renné University Hospital Würzburg Institute for Clinical Biochemistry and Pathobiochemistry Würtzburg, Germany
Zuhal Yapici Istanbul Faculty of Medicine Department of Neurology Istanbul, Turkey

Our proposal concerns a rare, potentially life-threatening swelling disease, named hereditary angioedema type III (HAE type III). In a collaborative effort between research groups from Germany, France, and Italy, we plan to analyze the genetic basis and pathophysiology of HAE type III. In contrast to the well-understood hereditary angioedema types I and II that are due to hereditary deficiency of C1 esterase inhibitor (a plasma protease inhibitor, which targets plasma kallikrein), this inherited disease is described exclusively in women. As a result of a successful collaboration between the research groups that submit the current proposal, we could recently identify the first genetic defect associated with this severe disease, single point mutations in the gene of coagulation factor XII (Hageman factor, Cichon et al., Am J. Hum Genetics, 2006). Clotting factor XII initiates the intrinsic pathway of coagulation and triggers formation of the inflammatory mediator bradykinin.

Strikingly, our research results clearly indicate that only a relatively small fraction of hereditary angioedema type III cases can be attributed to coagulation factor XII. It is evident that other, so far unknown genes, must play a role in disease development. Identification of these genes is one goal of the proposed project. Combining the family and patient samples collected by the participating groups, we have very high chances to successfully identify such genes.

In parallel to these genetic analyses, we will focus on characterizing the pathomechanism of the factor XII-associated hereditary angioedema type III using edema-formation models in genetically altered mice. These studies will provide an in-depth understanding of the molecular causes for angioedema type III. This project offers the unique chance to identify new targets to fight hereditary angioedema and to develop convenient tools for predictive testing of the disease. It may also open new avenues for edema therapy in other disease states such as diabetic retinopathy, asthmatic disease or inflammation. We believe that our project proposal fits very well with the goals envisaged by the E-RARE programme.

E-Rare 2012 - Created by Toussaint Biger