There are estimated to be more than 7000 rare genetic diseases (RGDs), which are defined as affecting less than 1 in 2000 people in Europe, many of which are monogenic. Although rare individually, collectively they affect 1 in 50 individuals. Diagnosis of these diseases is often very difficult and patients can remain undiagnosed or diagnosis can involve years of testing, worry and frustration. In 2013, in the UK, the ‘100 000 Genomes Project1 was launched to determine if whole genome sequencing could be beneficial for the diagnosis of rare diseases. This project1 has had a remarkable impact, resulting in life changing diagnoses and immediate implications for treatment decisions for many patients.

Although currently the newborn dried blood spot screening programme in the UK tests for nine rare but serious conditions where early treatment/management can prevent severe disability or death, the team were struck by the number of children in the Project whose conditions had remained undiagnosed and whose lives could have been transformed by early diagnosis, and this resulted in the recommendation that every child admitted to intensive care without a clear cause should have genomic sequencing. Additionally, the group proposed a new study, to sequence the DNA of 100 000 newborns to test for around 200 treatable disorders: The Newborn Genomes Programme, the launch of which was announced by the UK Government in December 2022, to begin in 2023.

Currently, as one third of children with a rare disease will die before their fifth birthday, the majority of which can be treated with simple interventions of diet modification or vitamin supplementation, this study will be crucial in providing life-changing treatment at the earliest opportunity.

1 10,000 Genomes Project Pilot Investigators et al. 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care – Preliminary Report. N Engl J Med 2021;385(20):1868–1880 doi: 10.1056/NEJMoa2035790.