A collaborative study by Katherine Schon, led by Patrick Chinnery (both Clinical Neurosciences and MRC Mitochondrial Biology Unit), demonstrates that whole genome sequencing (WGS), from a single blood test, picks up 31% more cases of rare genetic disorders than standard tests, shortening the ‘diagnostic odyssey’ that affected families experience, and providing huge opportunities for future research.
Mitochondrial disorders are amongst the most common inherited diseases, but a genetic diagnosis is not possible in ~40% of patients, limiting genetic counselling and prevention. Patients with suspected mitochondrial disorders were recruited to the 100,000 Genomes Project in England between 2015 and 2018. In total, 345 participants had their whole genome sequenced. Clinical information was collected systematically with the commonest being delayed gross motor development, intellectual disability, muscle weakness and dysfunction (myopathy), seizures and drooping eyelid (ptosis).
Published in the British Medical Journal, the study identified a definite or probable genetic diagnosis in 98 families (31%). Standard tests, which are often more invasive, failed to reach these diagnoses. Six possible diagnoses (2% of the 98 families) were made. A total of 95 different genes were implicated.
Surprisingly, 62.5% of the diagnoses were actually non-mitochondrial disorders, with some having specific treatments. This happened because so many different diseases resemble mitochondrial disorders, making it very difficult to know which are which. The study highlights the implications for the integration of whole genome sequencing into healthcare so that the results can help guide clinical management and improve patient diagnosis and outcomes.