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.

International Kindler Syndrome Network

Project Coordinator

University Medical Center Freiburg Dermatology


Giovanna Zambruno Instituto Dermatologico Dell'Immacolata - IRCCS Laboratory of Molecular and Cell Biology Rome, Italy
Judith Fischer Centre National de Génotypage CNRG componente CNG Evry, France
Peter Bruckner University Hospital Münster Physiological Chemistry and Pathobiochemistry Münster, Germany
Reinhard Fässler Max Planck Institute of Biochemistry Molecular Medicine Martinsried, Germany

Publications of the KINDLERNET project

Major results of the project

Kindlernet is a multidisciplinary consortium dealing with the Kindler syndrome (KS), a very rare skin disorder caused by mutations in the FERMT1/KIND1 gene. The disease manifests with skin blistering, photosensitivity, progressive poikiloderma and mucosal involvement, and increased risk of epithelial cancer. Due to its rarity KS is not well known, but efficient molecular diagnostics, competent management and accurate information for medical professionals are mandatory to improve quality of life of affected individuals and to reduce medical costs. Understanding of molecular disease mechanisms of KS will not only deliver indirect information on normal functions of the skin but also form a basis for biologically valid therapy strategies. Besides, due to phenotypic similarity to other conditions, KS constitutes an optimal research model for other socio-economically important pathologies, such as (premature) aging, tissue atrophies, photosensitivity and carcinogenesis.
The work of this multidisciplinary consortium aimed at generating larger, well-characterized international KS patient cohorts as a basis for research and disease management. Kindlernet infrastructure includes a coordinating office, a website, a database with patient registry and material bank, clinical-diagnostic centers and research laboratories. The research goal was to address such questions combining clinical and molecular genetics, molecular and cell biology, structural and biochemical analysis of human cells / tissues and mouse models. These approaches were successful in assembling the largest KS patients cohort so far and in uncovering the causes and molecular disease mechanisms of KS.

The major results of the Kindlernet are:
1. The assembly of the largest KS patients cohort, so far
2. The delineation of the natural history of the disorder, including the progression of the features and the occurence of complications (e.g. mucosal stenoses, skin cancer)
3. The definition of molecular diagnostic criteria
4. The identification of a KS-like phenotype caused by a specific COL17A1 mutation
5. The elucidation of the paracrine cytokine mediated pathomechanisms of skin fibrosis and atrophy in KS
6. The generation of mouse models which validate many aspects of the human disease. These models will make the investigation of further disease mechanisms, as well as specific therapies, possible.
7. The isolation of focal adhesion suprastructures containing the entire continuum of components from the cytoskeletal F-actin, the adaptor proteins vinculin, talin, ILK, and kindlin-1 from epidermis and epidermal keratinocytes with anti-kindlin-1 immuno-beads.
8. The expression of kindlin-1 at high levels in eccrine sweat glands in human skin or mouse foot pads, might contribute to the dry skin- phenotype in KS.
9. Outlook for specific therapeutic approaches in KS: topical antiinflammatory treatment to prevent fibrosis, external application of urea and/or electrolytes for skin dryness.

E-Rare 2012 - Created by Toussaint Biger