Test could end uncertainty in inherited muscle diseases
Clockwise from left: Dr Ira Deveson, Dr Andre Reis, Associate Professor Kishore Kumar, and Dr Dennis Yeow
Getting a definitive diagnosis of an inherited muscle disease, such as muscular dystrophy, can be a hard and lengthy process, but researchers in Australia may have found a solution.
A team from the Garvan Institute of Medical Research in Darlinghurst, New South Wales, have used an emerging form of genetic sequencing to test people living with known or suspected inherited myopathies, including some for whom prior gene testing failed to identify a cause.
The result? More than a third of those unsolved cases were able to get a diagnosis, something that can sometimes take "years [and] sometimes decades" with standard testing for this large group of heterogeneous disorders, which can affect an estimated one in 1,700–4,500 people worldwide. They often have similar clinical features, such as a degraded ability to walk, swallow, or speak clearly.
Along with earlier diagnosis, the study could help advance understanding of the genetic basis of inherited myopathies and the development of new, targeted therapies.
Their study – published in the journal Nature Communications – describes the use of a technique, known as long-read 'nanopore' sequencing, which passes DNA strands through a tiny protein pore and measures real-time changes in electrical current that can be used to decode the genetic sequence.
As its name suggests, this technique reads much longer stretches of DNA than standard methods and can pick up complex genetic changes that older tests routinely miss, according to the researchers, who noted that most current tests look for only one kind of DNA change at a time.
Until now, no single test could detect all of these changes at once, a gap that long-read sequencing closes, they added.
Dr Ira Deveson, lab head at Garvan and co-senior author of the new paper, said: "Many muscle diseases have no available genetic test, and for others there is a separate test for each different gene involved. Here, we've shown that it's possible to test all genes at once, and that's a game-changer for someone who has been through years of inconclusive tests."
The scientists are working with NSW Health Pathology's Molecular Medicine Laboratory at Concord Hospital to bring the test into routine care, and hope that it could be available across Australia – which has an estimated 6,000 people living with this type of disease – in the next two years or so.
They also said the approach could be applied to other rare inherited conditions.
"The long-read technology we have applied in this test is disease-agnostic," said Deveson. "What we have shown for muscle disease could, in time, be built for many of the rare genetic conditions where people currently spend years searching for a name for what they have. That is where we want this to go."
