Mitochondrial disorders can be very diverse in how they present in patients, and as such are easily mistaken for other conditions. Researchers at the University of Cambridge found that WGS from a single blood test was able to provide a diagnosis in 31 percent more cases than current standard testing.
'We recommend that whole genome sequencing should be offered early and before invasive tests such as a muscle biopsy. All those patients would need to do is have a blood test, meaning that this could be offered across the whole country in an equitable way,' said lead author Professor Patrick Chinnery from the MRC Mitochondrial Biology Unit and the Department of Clinical Neurosciences at the University of Cambridge.
The study, published in the British Medical Journal, recruited families with suspected mitochondrial disease from the 100,000 genomes project between 2015 and 2018. Whole genomes were sequenced from 345 participants.
From WGS analysis, 98 families (31 percent of participants) received a definite or probable diagnosis that standard tests did not detect. More than half of these diagnoses were for non-mitochondrial conditions with superficially similar symptoms who would probably not have received a diagnosis without WGS.
'These patients were referred because of a suspected mitochondrial disease and the conventional diagnostic tests are specifically for mitochondrial diseases. Unless you consider these other possibilities, you won't diagnose them. Whole genome sequencing isn't restricted by that bias,' said Professor Chinnery.
Of the families who did receive a diagnosis of mitochondrial disease, most of the causal variants detected were in genes known to be associated with mitochondrial disease but the precise mutations were often unique to the family. The authors recommend that WGS should be routinely offered to all acutely unwell individuals who may have a mitochondrial disorder, an option that at the moment is only available to acutely unwell children.
'A definitive genetic diagnosis can really help patients and their families, giving them access to tailored information about prognosis and treatment, genetic counselling and reproductive options including preimplantation genetic diagnosis or prenatal diagnosis' said co-author Dr Katherine Schon.