Hundreds of patients with rare diseases have been given a diagnosis for the first time, thanks to a study which involved analysing their entire genome.
More than 2,000 families took part and were recruited through the 100,000 Genomes Project, which started in 2013.
According to the scientists behind it, the approach can lead to better care, more focused treatments, and cost savings for the NHS.
Terri Hedley, who inherited a kidney condition from her father, was among those who received a new diagnosis.
Leslie had endured years of treatment for severe kidney disease, which resulted in two kidney transplants, and was concerned that his granddaughter Katie, as well as his daughter, would be affected.
However, after sequencing Leslie and Terri’s entire genome, it was discovered that she did not have the kidney problem.
“It was fantastic to know that it ends with me,” Terri, 41, said.
“She [Katie] is no longer required to have regular tests. We were very concerned about her.”
Terri’s daily life is unaffected by her kidney condition; however, her kidney function has deteriorated over the last 20 years.
A 10-year-old girl with a rare, unknown condition was also diagnosed as a result of the study, allowing her to receive a bone marrow transplant. She had been admitted to intensive care several times and had visited the hospital over 300 times.
Her siblings were tested, and no other family members were found to be at risk.
The study, led by Genomics England and Queen Mary University of London, is the first to use whole genome sequencing in a healthcare system and on a large number of patients with rare diseases.
Prof Sir Mark Caulfield of Queen Mary University of London, a former chief scientist at Genomics England, described it as a “major advance” that could be implemented globally at the first sign of symptoms.
He said the study paved the way for the technique being used in the NHS.
What is whole genome sequencing?
It is the process of analysing entire genomes, or all of the genes and DNA that comprise a human being.
Your genome is unique, has over three billion letters, and can be found in nearly every cell in your body.
Donating a sample of DNA, typically from a small blood sample, is required for genome sequencing.
A human genome can be sequenced in about a day, but it takes much longer to analyse.
The goal is to identify the differences between one person’s genome and a “reference” genome, which can number in the millions.
Most are harmless, but they are the reason we are different from each other.
Using clever software, scientists work out exactly which differences could be the cause of disease, and these are then fed back to the NHS and the patient.
What did the study find?
A quarter of those who participated in the study received a new diagnosis as a result of whole genome sequencing.
They were then able to receive better care, such as a diet change, vitamin supplementation, and other appropriate therapies. Other family members may also be screened for the same diagnosis.
A total of 14% of those diagnosed were discovered in regions of the genome that would have gone undetected by other methods of testing.
The following were the majority of the rare diseases discovered:
- eye conditions
- neurodevelopmental conditions
- metabolic conditions, which are related to diabetes, high blood pressure and obesity
The genes of 4,660 people from more than 2,100 families were analysed between 2014 and 2016 for the study, published in New England Journal of Medicine.
Many had gone through years of testing and appointments without getting any answers about the disease affecting their family. All were part of the 100,000 Genomes Project, led by Genomics England.
Are rare diseases always genetic?
Approximately 10,000 rare disorders affect approximately 6% of the population in Western societies.
More than 80% of these have a genetic component, and they are frequently disabling and costly to manage.
One-third of children with a rare disease die before reaching the age of five.
The new approach, according to Prof Damian Smedley of the Queen Mary research team, “was critical 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.”
Prof Chris Inglehearn, professor of molecular ophthalmology at the University of Leeds, stated that the findings demonstrated “beyond doubt” that human genome sequencing “can revolutionise medical care for a wide range of human diseases.”
However, he added that the 100,000 Genomes Project, which provided the study’s data, “can prove difficult for clinicians and researchers to access,” and that this needed to be addressed.
Another challenge, according to scientists, would be determining how whole genome sequencing could and should be used to identify rare diseases within the NHS.