Around 5,500 people with severe developmental disorders now know the genetic cause of their condition as a result of a major nationwide study that will help to improve diagnosis across the world. The study is published today in The New England Journal of Medicine.
The Deciphering Developmental Disorders study included more than 13,500 families from 24 regional genetics services across the UK and Ireland. The study is a collaboration between the NHS and the Wellcome Sanger Institute, and is funded by Wellcome and the Department of Health and Social Care.
All of the families who participated in the study had children with a severe developmental disorder, which was undiagnosed despite prior testing through their national health service and likely to be caused by a single genetic change. Researchers at the Wellcome Sanger Institute sequenced all the genes in both the children and the parents’ genomes to look for answers. While recruitment to the study has ended, the search for diagnoses in the study participants is still ongoing.
- diagnoses were made from changes in over 800 different genes, including 60 conditions that had been previously discovered by the study;
- around three-quarters of the conditions were caused by spontaneous mutations that were not inherited from either parent;
- the chances of success in getting a diagnosis were lower in families of non-European ancestry, reinforcing that it is imperative to increase research participation for under-represented groups.
Lead author Caroline Wright, Professor of Genomic Medicine at the University of Exeter, said ‘Getting the right diagnosis is absolutely critical for families with rare conditions, which collectively affect around 1 in 17 people. Most of the conditions are genetic and can be diagnosed using the same sequencing technology. The families in our study were desperate for answers, which can make a huge difference to clinical management and quality of life. We worked with hundreds of clinicians and scientists, as well as thousands of patients to try to find those answers. By sharing our findings, many more families in the future should get answers faster.’
Senior co-author Matthew Hurles, Head of Human Genetics and incoming Director of the Wellcome Sanger Institute, said ‘Undiagnosed patients with rare genetic diseases have the most to lose if they are not given an opportunity to participate in research and if their data are kept in silos. Many of these diagnoses were only made possible through combining data across all diagnostic centres in the UK and Ireland. For some diagnoses, it was only through sharing data with international colleagues that it was possible to make a diagnosis. As these genomic technologies move into routine healthcare, ensuring that undiagnosed patients can still benefit from research on their data will remain incredibly important.’
Senior co-author Helen Firth, Professor of Clinical Genomics at the University of Cambridge, Consultant in Clinical and Genomic Medicine at Cambridge University Hospitals NHS Foundation Trust, and lead clinician for the study, said ‘Embedding a powerful informatics platform at the heart of this study facilitated the collaboration with families, clinicians and scientists engaged in the project, and played a crucial role in its diagnostic success and in the discovery and ultimately treatment of new causes of rare genomic disease.’
Senior co-author Michael Parker, Professor of Bioethics at the Ethox Centre at Oxford Population Health, and ethics lead for the study, said ‘From the initial design of the study, through the building and sustaining of collaborative partnerships with clinicians, to the identification and addressing of practical ethical problems in real time throughout the life of the project, the embedding of ethics research and advice into the Deciphering Developmental Disorders project has been crucial to its success and to building and maintaining well-founded trust and confidence of clinicians and patients.’
Health Minister, Will Quince, said: ‘We’re creating the most advanced genomic healthcare system in the world and this study is yet another step forward to revolutionising care for NHS patients. Using cutting edge, high-tech methods such as this offers the potential to better understand and more accurately diagnose rare genetic conditions so children can access treatment faster and potentially limit the impact of the disease on their life.’
A similar approach to diagnosing individuals with rare diseases is now being used in the NHS by the Genomic Medicine Service, the Scottish Clinical Exome Sequencing Service, and the Rapid Genome Sequencing Service for acutely unwell children with a likely monogenic disorder, which can provide a genetic diagnosis for babies and children in or facing critical care within just ten days. The genetic disease causes identified in the current study will feed into the tests applied by the services, to help diagnose more people swiftly.