Researchers from the Wellcome Sanger Institute, along with collaborators from the University of Exeter and the University of Cambridge, have developed a new approach to potentially replace the current two-stop approach to diagnosing rare developmental disorders in paediatric patients.
The study, published in Genetics in Medicine and supported by Wellcome, the Health Innovation Challenge Fund and the Department of Health and Social Care (DHSC), shows that a single genetic test could enable earlier diagnosis and could save the NHS vital resources.
Developmental disorders such as attention-deficit/hyperactivity disorder, autism and cerebral palsy are impairments in a child’s physical, cognitive, language or behavioural development, impacting their daily functioning.
Researchers reassessed genetic data from nearly 10,000 families from the Deciphering Developmental Disorders (DDD) study to develop a single-assay approach, combining four algorithms using machine learning to analyse exome sequencing data, which reads protein-coding DNA.
Aiming to advance clinical genetic practice for paediatric patients with developmental disorders, the DDD study was established in 2010 and is funded by Wellcome and the DHSC, with support from the National Institute for Health and Care Research.
The team revealed that by using exome sequencing, the approach was as accurate, if not better, than standard microarrays – a genetic test that looks in detail at a person’s chromosomes to see if there are any extra or missing – at identifying disease-causing structural genetic variations.
The new approach, in comparison to current standard clinical methods, reliably detected 305 large-scale pathogenic mutations, including 91 that were previously undetectable using clinical microarrays.
Suggested to replace current methods, if adopted, the single genetic test could provide faster and more accurate diagnoses of rare genetic diseases, including cystic fibrosis and Duchenne muscular dystrophy and could save costs for the NHS.
Professor Matthew Hurles, director, Wellcome Sanger Institute, commented: “This study proves that with the right computational methods, a single test can accurately detect… how large-scale genetic variations impact human health”.
Caroline Wright, professor of genomic medicine, University of Exeter, said: “Using exome sequencing data to detect clinically important large-scale changes, at the same time as small genetic variants, marks a significant step forward in making genetic testing simpler, cheaper and more accessible.”