The Gene Dossier a Potted History

1. The Gene Dossier a Potted History Fiona Stewart

2. The Start • Was not very promising • Quite a lot of hostility to the idea that anyone would consider telling clinicians or laboratories who should have genetic tests and in what circumstances

3. First meeting of the steering group was on September 17th 2002

4. Gene Dossier Process • Laboratory decides it wishes to offer a test through the UKGTN • Gene dossier is down loaded from UKGTN website and completed • Gene dossier is submitted to UKGTN and is assessed • If approved goes onto the directory

5. The first gene dossier meeting • Involved the whole steering group • We were sent 80+ dossiers to consider prior to the meeting

8. The meeting • Probably fair to say there was a general feeling particularly amongst clinicians that if a test could ever be offered to anyone in any circumstances then it should be approved • No real feeling that we should define who the test was for and in what circumstances it might be appropriate to offer it (with a few exceptions!) • Pretty much all dossiers approved

9. Changes • Realised that it was impractical to have all GD’s considered by the entire steering group • Better to have a smaller group to consider the dossiers • Those that were approved would then go to the steering group for endorsement • A sub group was set up initially called the Gene Dossier Group now called the Genetic Test Evaluation Working Group

10. Composition of GD group • At least one of the following: • Clinical Geneticist • Clinical Scientist • Commissioner • Public Health • Genetic Counsellor • Patient Representative • UKGTN staff and the UKGTN expert clinical advisors

11. Single Gene Testing • Initially all GD’s were for one gene for one condition • Target population defined more carefully • Clinical indications for the test important • What was the clinical usefulness of the test? • What did this information add to the overall care and management of the patient and their family

12. Testing Criteria • Realised we had to define the population to whom the test should be offered • Also realised that there is a huge pressure on clinicians to offer a wide range of genetic tests to patients and some guidance about who might benefit most from the test would be helpful and might be welcomed by clinicians • Might also give some supportive evidence for cases where the clinician feels the test is not indicated • Testing criteria were introduced in 2006

14. Care Pathways • Very important to know where the genetic test fits into the investigative pathway • In conditions where there may be a number of genetic tests it is helpful to know in which order genes should be tested and what other tests and actions might be indicated • We started to ask laboratories to supply testing strategies in some cases

15. Our priority is to try and make things user friendly for the clinician • With the mainstreaming of genetic tests we know that some users will not be as familiar with the area of genetics • Therefore we feel testing strategies and testing criteria might be very useful

16. The Ultra Rares • We realised that a lot of time was being spent discussing dossiers for tests which might only be applicable to less than 5 patients per year • These tests are now first assessed by the expert advisors and come to the group for endorsement of their decision.

17. Panel Tests • We are receiving an increasing number of panel tests • These tests tend to use next generation sequencing and can look at a number of genes at once • They are particularly useful for conditions where a number of different genes can give a very similar if not identical clinical picture e.g. Retinitis pigmentosa

18. Costs • Although the cost of the panel test may be higher than a single gene test they may avoid the need for serial genetic testing • A good example is hereditary sensory motor neuropathy. If an affected individual does not have the common PMP22 duplication then serial testing of all the other genes, each of which may have a low pick up rate, can be very costly

19. Advantages to Patients • It can be very time consuming to test genes sequentially so an ‘all at once’ strategy can provide a more rapid result for the patient

20. Important points • Coverage may not be optimal for all the genes so if there is clear indication that a single gene is likely to responsible it is best to test for that first • If a mutation is found then family follow up and/or prenatal diagnosis would be done using the single gene test not the panel test

21. The future..... • More panel tests • Whole exome sequencing • Whole genome sequencing

22. Principles • Right patient • Right test • Right time • These principles hold true whatever methodology is available now or in the future

23. Special thanks to all the members of the Genetic Testing and Evaluation Working Group who have spent many happy hours pouring over gene dossiers Also thanks to the expert advisors Mark , Su and Shehla who are truly experts and whose input is invaluable Finally thanks to Peta , Jacqui and Jane plus other members of the UKGTN who have provided such great support over the years