Title: RARE GENETIC SKIN DISEASES - Orphanet

Title: RARE GENETIC SKIN DISEASES: ADVANCING DIAGNOSIS, MANAGEMENT AND AWARENESS THROUGH A EUROPEAN NETWORK

Acronym: GENESKIN

Proposal number: FP6-512117

Duration: 36 months Starting date: 01/07/2005 Instrument: Coordination action

Summary Genetic skin diseases comprise almost 300 rare but often severe and even life-threatening diseases and syndromes. Despite recent identification of causative genes in a number of these disorders, the molecular bases of several others are still unknown, and often the function of the identified disease-gene products remains an unsolved mystery. In addition, disease number and rarity impair proper management, and no curative therapy is available. By bringing together clinicians, researchers and patient associations, GENESKIN aims to generate accessible knowledge and improve health care service structures for affected people. The focus is on five major disease categories: epithelial adhesion disorders, keratinization disorders, ectodermal dysplasias, connective tissue diseases, DNA repair disorders. For each group, a clinical and laboratory network will generate and disseminate: 1) a list of reference centers with services offered, 2) diagnostic questionnaires/protocols 3) gene cards, mutation database, diagnostic reagent lists, and ongoing clinical trial list. The research topics to be co-ordinated in GENESKIN deal with: i) improved early post-natal and pre-natal diagnosis by novel immunohistochemical/biochemical and molecular tests, ii) identification of new genes involved in genetic skin diseases by collecting a sizable number of biological samples, iii) definition of genotype-phenotype correlation and characterisation of newly identified gene product functions by creation of a sample databank. Knowledge dissemination and improved management will also be insured through the organisation of involved personnel training. Finally, pan-European communication among patients’ organisations, ethic committees, physicians and scientist will be promoted. The information regarding clinical/diagnostic protocols/lists, diagnostic and research tools and communication among different groups will be integrated and disseminated through a dedicated web site.

Background Genetic skin disorders encompass almost 300 different diseases and syndromes, most of which are severely disabling or life threatening and have a major impact on health care services and personnel. The number and rarity of these disorders (prevalence between 1:6,000 and <1:500,000 for each condition) hamper single centre (or country) studies aimed at their characterisation and cure. Despite the enormous progress of the last decade, the molecular basis of several of these diseases is still unknown, and in many cases the function of the known disease-gene products remains an unsolved mystery. Furthermore, no curative therapy is at present available for any form of genetic skin disease and pharmaceutical companies have limited or no interest in developing diagnostic and therapeutic strategies for these orphan diseases. A significant logistical problem is that only a few centres in Europe are in a position to try to deal with groups of these diseases and even then their expertise is limited to just a few specific conditions. Thus, expert knowledge for clinical and molecular diagnosis, for management and innovative therapy is isolated and scattered in an often uncoordinated way throughout

Orphanet Database. Network 2006http://www.orpha.net/data/prj/FR/geneskin.pdf


Europe. As a result patients experience significant difficulties to find experts and multidisciplinary healthcare teams specialised in clinical and molecular diagnosis and able to offer high quality disease management. This situation can only be overcome by a European mobilisation of activities and resources, most effectively through a European Consortium that will facilitate development of substantially improved and cost-effective health care services.


The present project arises as a joined effort of European scientists and clinicians, with the direct involvement of patients’ associations, to establish a Consortium of groups engaged in providing a critical mass of patients and research tools in the fields of inherited skin diseases, including diseases predisposing to skin cancer. To this regard, the project main objectives are:

• To create a European clinical and diagnostic network for five major groups of genetic skin diseases, namely epithelial adhesion disorders, keratinization disorders, ectodermal dysplasias, connective tissue diseases, and DNA repair diseases;

• To integrate, test and validate diagnostic and research tools for the above mentioned disease groups;

• To promote training on clinical, diagnostic and management aspects of specific disease groups;

• To promote pan-European communication pathways among patients’ organizations, ethic committees, physicians and scientists.

Expected results:

• A web-based informatic platform that, for each of the five categories of diseases listed above, will contain: 1) a list of reference centers with clinical/diagnostic services offered; 2) diagnostic questionnaires/protocols/check-lists; 3) gene cards and mutation database; 4) lists of available diagnostic reagents; 5) disease-related web-sites and ongoing clinical trials; 6) recent up-dates in the proper field;

• For selected diseases: 1) standardized immunohistochemical/biochemical screening tests, preliminary to molecular diagnosis; 2) standardized prenatal and postnatal molecular diagnostic tests and a prototype assay based on microchip technology; 3) a “virtual” biological sample databank;

• Dissemination of knowledge about clinical features, diagnostic procedures and management of specific diseases groups at an European scale;

• Close alliance of patients’ organisations and ethic experts with physicians and scientists.

Potential applications: The achievement of the proposed objectives will greatly contribute to the implementation of the Community Policy Objective aimed at combating rare diseases. In fact, bypassing the problems related to the rarity of inherited skin diseases, the clinical and research network will provide a rapid translation of emerging gene discovery and gene function findings into clinical applications that are relevant to accurate, rapid and early diagnosis, molecular and prenatal testing, and to foster implementation of clinical trials. In

2 Orphanet Database. Network 2006http://www.orpha.net/data/prj/FR/geneskin.pdf

particular, the multidisciplinary synergistic efforts of investigators and clinicians, in close collaboration with patient associations, will allow:


the establishment of a real European task force for the study of these rare disorders at both the fundamental and clinical level;

• the rapid translation of the novel knowledge and diagnostic tools from the bench to the bedside, resulting in an improved diagnosis and management of these disorders both at the European and national scale;

• the augmentation of an early and accurate pre- and post-natal diagnosis, which is crucial for prognosis definition and proper management, and is beneficial for the psychological well-being of patients and families who do not feel well living in diagnostic uncertainty and insecurity;

• an easier access of patients to clinical trials and in general earlier and proper management leading to an increase of the quality of life of the patients, and improvement of the clinical course of the disease. This will reflect positively over the duration of life expectancy and medical costs.

In addition, close co-operation of physicians and scientists with public non-medical groups, i.e. patients organisations and ethic committees will contribute:

• to develop and maintain an equal dialog among these different parts;

• patient specific needs to be continuously part of medical and/or scientific decisions, in agreement with ethical values;

• to further raise public awareness about rare diseases, fulfilling societal goals.

Key words: Rare genetic diseases, skin, dermatology, diagnosis.


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Partner 1

A Dr. Giovanna Zambruno Provincia Italiana della Congregazione dei Figli dell’Immacolata Concezione-I.D.I-I.R.C.C.S. Laboratory of Molecular and Cell Biology Via dei Monti di Creta 104, 00167 Rome, Italy

B Dr. Giandomenico Russo Provincia Italiana della Congregazione dei Figli dell’Immacolata Concezione-I.D.I-


Laboratory of Cancer Genetics Via dei Monti di Creta 104, 00167 Rome, Italy

Partner 2

A Dr. Miria Stefanini Consiglio Nazionale delle Ricerche Istituto di Genetica Molecolare Via Abbiategrasso 207, 27100 Pavia, Italy

B Dr. Michele D’Urso Consiglio Nazionale delle Ricerche Istituto di Genetica e Biofisica "Adriano Buzzati Traverso" - Laboratory of Human Genetics Via Pietro Castellino, 111, 80131 Naples, Italy

Partner 3

Prof. Ivonne Ronchetti Università di Modena e Reggio Emilia Department of Biomedical Sciences Via Campi 287, 41100 Modena, Italy

Partner 4

Prof. Leena Bruckner-Tuderman Universitaetsklinik Freiburg University Hospital Freiburg - Department of Dermatology Hauptstrasse 7, 79104 Freiburg, Germany

Partner 5

Prof. Heiko Traupe University Hospital Muenster University of Muenster - Department of Dermatology von-Esmarch-Str. 58, 48149 Münster, Germany


Partner 6

Dr. Hans Christian HenniesUniversity of Cologne – University HospitalCentre for Functional GenomicsZulpicher Str. 47, 50674 Cologne, Germany

Partner 7

Prof. Karl-Heinz Grzeschik Philipps-Universitaet Marburg Institut fuer Allgemeine Humangenetik der Philipps-Universitaet Marburg Bahnhofstrasse 7, 35037 Marburg, Germany

Partner 8

Prof. John Alexander McGrath Kings College London Genetic Skin Disease Group, The Guy's, King's College and St Thomas'Hospitals' Medical School Lambeth Palace Road SE1 7EH London, United Kingdom

Partner 9

A Prof. Irene May Leigh Queen Mary & Westfield College Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and the London Medical School, Queen Mary 2 Newark Street, E1 2AT London, United Kingdom

B Prof. David Peter Kelsell Queen Mary & Westfield College Centre for Cutaneous Research, Institute of Cell and Molecular Science, Barts and the London Medical School, Queen Mary 2 Newark Street, E1 2AT London, United Kingdom

Partner 10

Orphanet Database. Network 2006http://www.orpha.net/data/prj/FR/geneskin.pdf 6 Orphanet Database. Network 2006http://www.orpha.net/data/prj/FR/geneskin.pdf

Partner 11

Dr. Malcom B. Hodgins University of Glasgow Cancer Sciences and Molecular Pathology University Avenue, G12 8QQ Glasgow, Scotland - United Kingdom

Partner 12

Mr. John Richard William Dart DebRA Europe DEBRA House, 13 Wellington Business Park, Dukes Ride, RG45 6LS Crowthorne, U.K.

Partner 13

Dr. Alan David Irvine Our Lady’s Hospital for Sick Children Department of Paediatric Dermatology – Our Lady’s Hospital, Crumlin Cooley Road, Crumlin, D4 Dublin, Ireland

Partner 14

A Dr. Guerrino Meneguzzi Institut National de la Santé et de la Recherche Médicale INSERM Unité 634 27 Avenue Valombrose, 06107 Nice, Cedex 02, France

B Prof. Alain Hovnanian Institut National de la Santé et de la Recherche Médicale INSERM Unité 563 - Department of Functional Genetics of Epithelial Diseases Allée Honoré Serres, Pavillon Levebvre, 31024 Toulouse, Cedex 3, France

C Prof. Alain Taieb Institut National de la Santé et de la Recherche Médicale INSERM Unité 217 – Department of Dermatology, Université Victor Segalen 146, rue Léo Saignat 33076 Bordeaux, Cedex, France


Prof. Jean-Paul Ortonne Centre Hospitalier Universitaire de Nice Service de Dermatologie 151 route de Saint Antoine de Ginetière, 06202 Nice, Cedex 3, France


Partner 16

Dr. Alain Sarasin Centre National de la Recherche Scientifique Laboratory of Genetic Instability and Cancer – UPR 2169-CNRS Institut Gustave Roussy 39 rue Camille Desmoulins, 94805 Villejuif, France

Partner 17

Prof. Christine BodemerAssistance Publique – Hopitaux de ParisHopital Necker Enfants Malades - Service de Dermatologie149 rue de Sevres, 75743 Paris, Cedex 15, France

Partner 18

Dr. Judith Fischer Consortium National de Recherche en Genomique Centre National de Genotypage - Department of Dermatological Diseases 2, rue Gaston Cremieux, 91057 Evry, Cedex, France

Partner 19

Prof. Daniel HohlHospices Cantonaux - Centre Hospitalier Universitaire VaudoisService de Dermatologie des HospicesAv de Beaumont 29, 1011 Lausanne, Switzerland

Partner 20

Prof. Anne De PaepeUniversiteit GentDepartment Medical Genetics - Ghent University HospitalDe Pintelaan 185, 9000 Gent, Belgium

Partner 21

Prof. Jan H.J. HoeijmakersErasmus Medical Center RotterdamMedical Genetic Cluster - Department of Cell Biology & GeneticsDr. Molewaterplein 50, 3000 DR Rotterdam, Netherlands


Partner 22

Prof. Marcel F. JonkmanRijksuniversiteit GroningenDepartment of DermatologyHanzeplein 1, 9700RB Groningen, Netherlands

Partner 23

Dr. Antonio Bernad Asociacion de Epidermolisis Bullosa de Espana Consejo Superior de Investigaciones Cientificas Centro Nacional de Biotecnologia Departamento de Inmunologia y Oncologia. Campus Universidad Autonoma de Madrid – Cantoblanco, 28049 Madrid, Spain

Partner 24

Prof. Robert StrohalFederal Academic Hospital of FeldkirchDepartment of DermatologyCarinagasse 47, 6800 Feldkirch, Austria

Partner 25

Prof. Johann W. BauerGemeinnutzige Salzburger Landeskliniken Betriebsgesellschaft mbHDermatology -LaboratoriesMullner Haupstrasse 48, A-5020 Salzburg, Austria

Partner 26

Prof. Sarolta KarpatiDept. of Dermato-Venereology – Semmelweis UniversityMaria u. 41, 1085 Budapest, Hungary

Partner 27

Prof. Anders Vahlquist, MD, PhDDepartment of Medical Sciences /Dermatology and Venereology/Hudkliniken, University HospitalS-751 85 Uppsala, Sweden


Title: RARE GENETIC SKIN DISEASES - Orphanet

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