A study has shown that whole genome sequencing could help save the NHS millions of dollars. It was used to diagnose rare diseases in 25% of patients.
Some families have found that the results have given them reassurance, while others have been able to inspire life-altering treatments.
Rare inherited diseases, which are rare, affect approximately 6% of the UK's population. This is roughly 3 million people. Geneticists used to look at the person's genome through a microscope in order to find the abnormalities. However, this is not able to spot small, but often very significant, changes such as single letter substitutions within the genetic code.
This is why "many people with rare diseases either live very long diagnostic odysseys in order to find an answer for why or do not get an explanation in their entire lives", stated Prof Sir Mark Caulfield, Queen Mary University of London (QMUL), a former chief scientist at Genomics England.
The 100,000 Genomes Project was launched by the UK government in 2013. It aimed to determine if WGS, which is the process of reading through all 3bn letters of the human genome, could help doctors better understand patients' symptoms and identify family members at risk. NHS England was the first national health system to offer WGS as part of routine care to patients with rare and undiagnosed cancers five years later.
This study, published in The New England Journal of Medicine, examines the diagnostic and clinical effects of genetic sequencing within a national health system. Caulfield and Prof Damian Smedley (also at QMUL) analysed the genomes from 4,660 individuals from 2,183 families. They were all early participants to the 100,000 Genomes Project. They sought out rare genetic variants to explain their conditions.
This led to a new diagnosis for 25% of patients, many of whom had undergone years of medical evaluations without satisfactory answers. In 25% of these cases, it resulted in more targeted care such as family screening, provision of vitamins or minerals, and other therapies to help manage their condition.
Certain conditions, such as intellectual disability and vision or hearing disorders, had a diagnostic yield of 40-55%.
Terri Hedley is a 41-year old paramedic from Newcastle upon Tyne who has benefited from the program. Her father, Leslie had to endure years of treatment for a serious renal disease. Two kidney transplants were performed and his uncle died from kidney failure. Hedley was also diagnosed with kidney disease at 21.
She has been on medication for the past 20 years. However, her kidney function has declined recently and she may need a transplant. Her greatest fear was that her condition might have been passed on to Katie, who is now 20. It was impossible to test Katie for the condition as she did not know the cause. WGS identified the gene that caused the family's problems and confirmed Katie was not carrying it.
Hedley stated: "It's been amazing to discover that Katie won't have to go through all my dad went through and what I might be facing in the future." This means that my kidney problems are now essentially over.
A separate case involved a genomic analysis of a four-month-old boy who died from complications resulting from a failure to transport vitamin B12 into the cells. The younger brother was able to identify the genetic anomaly and receive weekly vitamin B12 injections to stop his disease from progressing.
WGS can improve the lives of patients and save hundreds of thousands of pounds. The NHS was estimated to have spent PS356,571 on a 10-year old girl who had to endure multiple hospital visits and intensive care during her seven-year diagnostic journey. After genome sequencing revealed her problem, the bone-marrow transplant that healed her cost PS70,000.
Smedley stated that this is the first time whole genome sequencing has been integrated into rare disease diagnostics within a healthcare system such as the NHS. It can be applied at scale to all forms of rare diseases. This study supports whole genome sequencing being the preferred genetic test for rare diseases patients in healthcare systems around the world.
WGS has been very helpful for 25% of patients who have received a diagnosis. However, 75% are still waiting for answers. Their genome sequences are stored in a database so that researchers can continue to learn about the genetic basis of the disease.
