Single DNA test can screen for over 50 genetic diseases

A new DNA test, developed by a research team led by Sydney’s Garvan Institute of Medical Research, has been shown to identify a range of hard-to-diagnose neurological and neuromuscular genetic diseases quicker and more accurately than existing tests. The test has been described in the journal Science Advances.

The diseases covered by the test belong to a class of over 50 diseases caused by unusually long repetitive DNA sequences in a person’s gene, known as short tandem repeat expansion disorders. As explained by Dr Ira Deveson, Head of Genomics Technologies at the Garvan Institute, these diseases are “often difficult to diagnose, due to the complex symptoms that patients present with; the challenging nature of these repetitive sequences; and limitations of existing genetic testing methods”.

Repeat expansion disorders can be passed on through families, can be life-threatening and generally involve muscle and nerve damage, as well as other complications throughout the body. Yet according to Dr Kishore Kumar, a co-author of the study and neurologist at Concord Hospital and the University of Sydney, current genetic testing for expansion disorders can be hit and miss.

“When patients present with symptoms, it can be difficult to tell which of these 50-plus genetic expansions they might have, so their doctor must decide which genes to test for based on the person’s symptoms and family history,” Dr Kumar said. “If that test comes back negative, the patient is left without answers. This testing can go on for years without finding the genes implicated in their disease. We call this the ‘diagnostic odyssey’, and it can be quite stressful for patients and their families.

“This new test will completely revolutionise how we diagnose these diseases, since we can now test for all the disorders at once with a single DNA test and give a clear genetic diagnosis, helping patients avoid years of unnecessary muscle or nerve biopsies for diseases they don’t have, or risky treatments that suppress their immune system,” Dr Kumar said. Although repeat expansion disorders cannot be cured, a quicker diagnosis can help doctors identify and treat disease complications earlier, such as heart issues associated with Friedreich’s ataxia.

Using a single DNA sample, usually extracted from blood, the new test works by scanning a patient’s genome using a technology called Nanopore sequencing. Dr Deveson said, “We’ve programmed the Nanopore device to hone in on the roughly 40 genes known to be involved in these disorders and to read through the long, repeated DNA sequences that cause disease.

“By unravelling the two strands of DNA and reading the repeated letter sequences (combinations of A, T, G or C), we can scan for abnormally long repeats within the patient’s genes, which are the hallmarks of disease.

“In the one test, we can search for every known disease-causing repeat expansion sequence, and potentially discover novel sequences likely to be involved in diseases that have not yet been described.”

The study saw the researchers correctly diagnose all patients with conditions that were already known, including Huntington’s disease, fragile X syndrome, hereditary cerebellar ataxias, myotonic dystrophies, myoclonic epilepsies, motor neuron disease and more. Furthermore, the Nanopore technology used in the test is smaller and cheaper than standard tests, which the team hopes will smooth its uptake into pathology labs.

“With Nanopore, the gene sequencing device has been reduced from the size of a fridge to the size of a stapler, and costs around $1000, compared with hundreds of thousands needed for mainstream DNA sequencing technologies,” Dr Deveson said.

The team expects to see their new technology used in diagnostic practice within the next 2–5 years. One of the key steps towards that goal is to gain appropriate clinical accreditation for the method. Once accredited, the test will also transform research into genetic diseases, said study co-author Dr Gina Ravenscroft from the Harry Perkins Institute of Medical Research.

“Adult-onset genetic disorders haven’t received as much research attention as those that appear in early life,” Dr Ravenscroft said. “By finding more people with these rare adult-onset diseases, and those who may be pre-symptomatic, we’ll be able to learn more about a whole range of rare diseases through cohort studies, which would otherwise be hard to do.”

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