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DNA double helix

A world-first study involving HERC researchers has found that using whole-genome sequencing could transform the lives of patients with rare diseases and save the NHS millions of pounds. The study has been published today in the New England Journal of Medicine.

Rare diseases are a global health challenge, with around 10,000 disorders affecting 6% percent of people in Western societies. Over 80% of these diseases have a genetic basis, but because these are often tiny errors in a person’s DNA they can easily be missed by conventional diagnostic techniques (e.g. studying the person’s chromosomes through a microscope). One third of children with a rare disease die before their fifth birthday.

In 2013, the UK Government launched the 100,000 Genomes Project, to investigate whether whole-genome sequencing (where all three billion base pairs of a person’s genome are sequenced) could improve diagnosis and treatment for patients with rare diseases. The project aimed to sequence 100,000 genomes from around 85,000 NHS patients affected by a rare disease, or cancer. In this pilot study, 4,660 participants from 2,183 families were recruited, all of whom were affected by an undiagnosed rare disease.

Key results

  • Using whole-genome sequencing led to a new diagnosis for 25% of the participants.
  • Of these new diagnoses, 14% were found in regions of the genome that would be missed by other conventional methods, including other types of non-whole genomic tests. For certain conditions, including intellectual disability, hearing conditions and vision disorder, the rate of new diagnoses was even higher, at 40-55%.
  • The most common types of rare diseases identified were eye conditions, neurodevelopmental conditions, and metabolic conditions.

For many of the participants, a diagnosis from whole-genome sequencing ended years of living in uncertainty without a definite answer. The median duration of these ‘diagnostic odysseys’ was 75 months, and the median number of hospital visits undertaken during this time was 68. Around 25% of patients who received a new diagnosis were then able to receive focused clinical care, including dietary change, provision of vitamins and / or minerals, and other therapies.

The new diagnoses also enabled family members to be tested for the same condition, to provide reassurance that the disease had not been passed on to other children, or to enable preventative therapies if it had.

Researchers from HERC undertook a costing analysis as part of this study to provide some initial estimates of the potential impact of whole genome sequencing on healthcare resource use and costs for the NHS. This found that patients in the study had more than 180,000 hospital visits at a combined cost of around £87 million to the NHS.

Dr James Buchanan said: ‘The findings from our study show that whole-genome sequencing can have significant impacts, both in transforming people’s lives and reducing NHS costs. For instance, one participant, a 10-year-old girl, had endured a seven-year search for a diagnosis, involving over 300 hospital visits at a cost of £356,571. But a diagnosis from whole-genome sequencing enabled her to receive a curative bone marrow transplant, costing £70,000. This diagnosis also meant that her siblings could undergo predictive testing, which showed they were not at risk of the same disorder.’

Professor Sarah Wordsworth added: ‘The study is the first to analyse the diagnostic and clinical impact of whole-genome sequencing for a broad range of rare diseases within a national healthcare system. The findings support its widespread adoption for many rare diseases in health systems worldwide.’

The study was led by Genomics England and Queen Mary University of London and undertaken in partnership with the National Institute for Health Research (NIHR) BioResource and Illumina (who conducted the sequencing). It was funded by the NIHR, Wellcome, the Medical Research Council, Cancer Research UK, the Department of Health and Social Care, and NHS England. Professor Wordsworth and Dr Buchanan were also supported by funding from the NIHR Oxford Biomedical Research Centre.