Whole genome sequencing can successfully be used to diagnose previously unrecognised rare diseases, according to a major British research project.
The study found a disease that was treated with a bone marrow transplant and a genetic condition causing kidney disease – among other findings, the researchers reported in the New England Journal of Medicine.
The project was led by Genomics England and Queen Mary, University of London, and has involved 4,660 members of 2,183 families, all searching for information about serious undiagnosed health problems.
Researchers said the study led to a new diagnosis for 25% of participants – and 14% of these were found in regions of the genome that would not have been identified by any other existing technique.
The project led to a girl aged ten receiving a bone marrow transplant after seven years of searching for a diagnosis for a condition that had led her to need more than 300 hospital admissions.
In a second instance two infant siblings were diagnosed with a metabolic disorder that could be treated with weekly vitamin B12 injections. One child had already died by the time the discovery was made.
Researcher Professor Sir Mark Caulfield said: “We hope this major advance will enable rare disease patients worldwide to start receiving diagnostic whole genome sequencing where appropriate. Our findings show that deployment of this comprehensive and efficient genomic test at the first signs of symptoms, can improve diagnostic rates.”
Fellow researcher Professor Damian Smedley said: “This is the first time that whole genome sequencing has been directly embedded into rare disease diagnostics in a healthcare system like the NHS and applied at scale across the full breadth of rare disease. Our novel software, together with collection of detailed clinical data, was key to us being able to solve the needle in a haystack challenge of finding the cause of a rare disease patient’s condition amongst the millions of variants in every genome. A large proportion of the diagnoses we discovered were found outside the coding region and would not have been detected by existing approaches.
“This study makes the case for healthcare systems worldwide to adopt whole genome sequencing as the genetic test of choice for rare disease patients.”
Dr Richard Scott, Chief Medical Officer at Genomics England, added: “Historically, diagnosis of rare diseases has often been reliant on clinicians doing multiple different targeted tests – an approach that can delay diagnosis and access to more tailored care. Improved knowledge of genomics and the whole genome sequencing and data infrastructure that the government and NHS have invested in now offers us the ability to radically transform the process.
“This paper provides evidence of that transformation and where it has most impact.”
100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care – Preliminary Report. NEJM 11 November 2021
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