Whole Genome Sequencing Could Save NHS Millions of Pounds, Study Finds | Genetic

The use of whole genome sequencing could save the NHS millions of pounds, a study suggests, after finding that a quarter of people with rare diseases have been diagnosed with their condition using technology.

In some cases, the results reassured families that they had not passed on their disease to their children, while in others, they inspired life-changing treatments.

Although individually rare, rare inherited diseases affect around 6% of the UK population, or around 3 million people. Traditionally, geneticists have looked for abnormalities underlying such conditions by examining a person’s chromosomes under a microscope, but this fails to spot tiny, but often very large, changes, such as single letter substitutions in the genetic code.

For this reason, “many people with a rare disease either go through very long diagnostic odysseys to get an answer as to why they are the way they are, or they don’t get a response in their entire lives,” said Professor Sir Mark Caulfield. To Queen Mary University of London (QMUL), former Chief Scientist of Genomics England.

In 2013, the British government launched the 100,000 genomes project to determine whether WGS – which involves reading the entire 3 billion letter pairs of the human genome – could help doctors better understand the cause of patients’ symptoms and identify other family members who may be at risk . Five years later, NHS England became the first national health system in the world to offer WGS to people with rare undiagnosed diseases and cancer as part of routine care.

The study, published in the New England Journal of Medicine, is the first to analyze the diagnostic and clinical impact of such genetic sequencing within a national health system. Researchers led by Caulfield and Professor Damian Smedley, also at QMUL, analyzed the genomes of 4,660 people from 2,183 families – all of the original 100,000 genomes participants – for rare genetic variants that could explain their conditions .

This led to a new diagnosis in 25% of the patients – many of whom had undergone years of medical evaluations without satisfactory responses – and in a quarter of those cases, it enabled them to receive more targeted care, such as a additional family screening, the provision of vitamin or mineral supplements, or other therapies to help them manage their condition.

For some conditions, including intellectual disability, vision and hearing impairments, the diagnostic yield was even higher, at 40-55%.

Among those who have benefited is Terri Hedley, a 41-year-old paramedic from Newcastle upon Tyne, whose father, Leslie, endured years of treatment for severe kidney disease, including two kidney transplants, and whose uncle also died of kidney failure. Hedley was also diagnosed with kidney problems at the age of 21.

For the past two decades she has been on medication, but recently her kidney function has deteriorated and she may also need a transplant. Her biggest fear was that she might have passed the disease on to her 20-year-old daughter Katie. But without knowing the cause of their illness, there was no way to test it. WGS has now identified the gene responsible for the family’s problems and revealed that Katie does not carry it.

Hedley said: “It has been fantastic to find out that Katie won’t have to go through everything my dad has been through and what I may be going through in the future. This means that the kidney problems basically stop with me.

In a separate case, genomic analysis of a baby boy who died at the age of four months revealed that his problems were caused by an inability to transport vitamin B12 into his cells. The identification of this genetic defect led to his younger brother being diagnosed with the same problem within days of his birth and indicated an effective treatment: weekly injections of vitamin B12 which kept his disease from progressing.

In addition to improving the lives of patients, the WGS can also free up NHS services, saving hundreds of thousands of pounds in some cases. For example, it is estimated that a 10-year-old girl who had multiple hospital visits and intensive care admissions during her seven-year diagnostic odyssey cost the NHS £ 356,571. Once genome sequencing identified her underlying problem, the bone marrow transplant that cured her cost £ 70,000.

Smedley said: “This is the first time that whole genome sequencing has been directly integrated into rare disease diagnostics in a healthcare system like the NHS and applied widely across the spectrum of rare diseases. This study advocates for healthcare systems around the world to adopt whole genome sequencing as the genetic test of choice for patients with rare diseases. “

As helpful as the WGS has been for the 25% of patients diagnosed, that still leaves 75% still waiting for answers. Because their genomic sequences have been stored in a database, the hope is that other diagnoses will emerge as researchers learn more about the genetic basis of the disease.