Personalising whole genome sequencing could double the diagnostic rates of rare diseases, according to a new UK study.
Research led by a team at UCL say their findings provide a “significant step forward” in providing some answers for people with rare genetic diseases for whom the molecular cause of their medical problems remains unknown.
In the study, published in Nature Communications, researchers at The London Mitochondrial Centre at UCL Queen Square Institute of Neurology and UCL Great Ormond Street Institute of Child Health tested how using a genomic medicine team of specialist doctors, bioinformaticians, and scientists could boost the capabilities of NHS diagnostic laboratories beyond the standard semi-automated analysis of data.
They re-evaluated undiagnosed cases to identify clues that could help towards a more personalised analysis, applying additional bioinformatic approaches and using advanced computer technologies to identify genetic alterations in a patients’ DNA, which may have been overlooked in routine testing.
They analysed 102 undiagnosed patients, who were believed to have a primary mitochondrial disease and who had undergone whole genome sequencing via the NHS’s 100,000 Genomes Project.
The personalised approach increased the diagnostic rate from 16.7% to 31.4% and also detected potential disease-causing variants in a further 3.9% of patients.
Lead author Dr Robert Pitceathly, co-lead for the London NHS Highly Specialised Service for Rare Mitochondrial Disorders and a research group leader at UCL Queen Square Institute of Neurology, said: “The NHS has invested heavily in advanced genetic technologies. Consequently, the UK has established itself at the forefront of diagnostic whole genome sequencing.
“That said, some people with rare genetic diseases remain without a molecular diagnosis after their genome is analysed.
“We believe investing in specialist genomic medicine teams is crucial, ensuring equitable access to dedicated multidisciplinary expertise and maximising diagnoses.
“On average, patients in our study waited over 30 years for a diagnosis – we now have the capability to solve such cases but need adequate workforce planning to support NHS diagnostic genetic laboratories in achieving this goal.”
He added that every new genetic diagnosis had a direct impact on patient care, including additional check-ups for heart problems, hearing loss, and diabetes, and access to clinical trials.
Professor Michael Hanna, director of UCL Queen Square Institute of Neurology said: “This work is a significant step forward in developing the best ways to maximise the benefits of genome analysis for patients.
“It clearly demonstrates that by combining automated approaches to genome analysis with data interpretation by a skilled multidisciplinary team the diagnostic rates doubles. This is an important finding that will influence how genomic medicine diagnostic services should evolve worldwide.”
Macken WL, Falabella M, McKittrick C et al. Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing. Nature Communications 7 November 2022
Leave a Reply