1. Prof. Timothy Barrett Euro-WABB Project Leader Ms. Amy Farmer Euro-WABB Project Manager www.euro-wabb.org Euro-wabb@bch.nhs.uk

2. The Problem: Different combinations of symptoms Rare Disease Day 2012 - Rare but Strong Together Diabetes Vision loss Hearing loss ObesityCardiomyopathy Common diabetes Isolated vision impairment Non-syndromic deafness Common obesity Isolated cardiomyopathy WARNING !!! Failure to diagnose patterns Too rare for doctors to learn Little or no research Inadequate patient information Failure to treat properly WARNING!!!

3. Funded by the European Union in the Framework of the Health Programme (contract ref: 2010-12-05) 3 year project which began on 01/01/2011 9 Associate Partners across Europe European Rare Diseases Registry collecting clinical and diagnostic data Wolfram, Alström and Bardet-Biedl (WABB) syndromes and other syndromes such as Wolcott-Rallison and Thiamine-Responsive Megaloblastic Anaemia (TRMA) Project activities divided into 6 work packages: coordination, dissemination, evaluation; genetics, clinical guidelines, and rare disease European Registry

4. The WABB diseases Wolfram Childhood diabetes, optic atrophy, deafness, neuro-degeneration Alström Obesity, retinal dystrophy, deafness, often cardiomyopathy and diabetes Bardet-Biedl Obesity, retinal dystrophy, deafness, often diabetes, polydactyly, cystic kidneys Plus: Wolcott-Rollison syndrome Roger’s syndrome Other even rarer syndromes

5. Objectives To support efficient diagnosis, treatment, and research for WABB diseases in Europe 1.To identify barriers to doctors using an EU-wide registry 2.To agree data to collect on each rare disease 3.To develop and road test a web based registry 4.To identify and catalogue all mutations for each disease and genotype/phenotype correlations 5.To assess patient information /professional learning needs 6.To write information for patients/professionals Common datasets WHO classification Mutation Database Diagnostic network Information/Education E.g. AS-UK handbook

6. Description of the project 300 anonymised patient records: medical, genetic, investigations, quality of life. State of the art security Clinical Partners: take consent from patients to input their data anonymously Patient partners: register themselves, see own data records, input quality of life data Outputs: Genetic testing network Natural history of WABB diseases Evidence based patient information Learning materials for health professionals Research Partners: Regulated access to data Platform for clinical trials No direct access to patients EU-WABB Registry

7. Value added of collaborating across Europe Value added: – Network of genetic testing laboratories – Critical mass to enable high quality research – Patient numbers for clinical trials Quicker progress to new treatments for these diseases – Sharing of best practice – Health professionals and Patient support groups working as partners Wolfram syndrome UK

8. Collaborative Links & Expressions of Interest

9. Identify and catalogue mutations (published & unpublished) in the RDS genes DiseaseOMIMMutated Gene(s)Database Wolfram syndrome 222300WFS1LOVD- ALMS1 Alström syndrome 203800ALMS1LOVD- WFS1 Bardet-Biedl syndrome 209900BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TCC8, BBS9, BBS10, TRIM32, BBS12, MKS1, CEP290 PENDING Thiamine- responsive megaloblastic anaemia 249270SLC19A2LOVD- SLC19A2 Wolcott- Rallison syndrome 226980EIF2AK3LOVD- EIF2AK3 Leiden Open source Variation Database (LOVD) software Current variants 1017, of which 358 are unique variants.

10. Supporting Equal Access to Genetic Testing CHU Nice, FRANCE Royal Devon and Exeter NHS Trust, UK Radboud University, Nijmegen Medical Centre, Netherlands North East Thames Regional Molecular Genetics Laboratory, UK Medical University of Lodz, Poland W A B O B W A Antwerp University Hospital, BELGIUM W West Midlands Regional Genetics Lab, UK W W O University of Padua, ITALY A Universidad de Vigo, SPAIN A A

11. EURO-WABB Registry https://registry.euro-wabb.org Web-based data collection undertaken by local clinician with input from patient or parent/guardian

12. Ethics: extract from UK form

13. 44 Data fields in the Core dataset 370 data fields in the Extended dataset Capturing clinical and molecular genetic features Onset of Symptoms Phenotyping information Standardised using ICD- 10 and ESPE Classification coding systems 44 Data fields in the Core dataset 370 data fields in the Extended dataset Capturing clinical and molecular genetic features Onset of Symptoms Phenotyping information Standardised using ICD- 10 and ESPE Classification coding systems

14. Selecting ‘Yes’ for a particular symptom prompts for further detail (ICD-10 code) and age of onset of symptoms

15. Local Participants

16. Current Recruitment UKPolandItalyTurkey Republic of Macedonia Czech RepublicKuwaitMalta Europe Total Alstrom104150000029 Wolfram121411211133 Bardet-Biedl170000000 Wolcott-Rallison200000002 TRMA000000000 41181612111 TOTAL81 Ethical approvals in place in Poland, Italy, Spain, Estonia and the UK Ethics applications underway in Germany, Denmark and France Collaborative links established with further sites keen to take part Total Registry Participants: 81

17. Acknowledgements: EURORDIS Mme. Nolwen Jaffre Associate Partners www.euro-wabb.org Thank you