Garvan Institute scientists have developed a new DNA test that has been shown to identify a range of hard-to- diagnose neurological and nuromuscular diseases.
Australian scientists have developed a single test for over 50 genetic diseases which will ‘cut diagnosis from decades to days’.
The medical researchers have shown how new genomic sequencing technology can reduce the ‘diagnostic odyssey’, experienced by people with rare neurological and neuromuscular diseases, that can take decades.
The single DNA test – developed by researchers at the Garvan Institute of Medical Research in Sydney and collaborators from Australia, UK and Israel – can screen a patient’s genome for over 50 genetic neurological and neuromuscular diseases such as Huntington’s disease, muscular dystrophies and fragile X syndrome. The research is published in the journal Science Advances and the team expects the test – which identifies the range of hard-to-diagnose genetic diseases quicker and more accurately than existing tests – to be ‘standard in pathology labs within the next two- to-five years’.
Senior study author Dr Ira Deveson, Head of Genomics Technologies at the Garvan Institute, noted: ‘We correctly diagnosed 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.’
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 genes, known as Short Tandem Repeat (STR) expansion disorders.
‘They 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,’ explained Dr Deveson.
Study participant, John, first realised ‘something was wrong’ when experiencing balance problems during a ski lesson.
He said: ‘It was very worrying having symptoms that, over the years, increased in severity – from being active and mobile to not being able to walk without support. I had test after test for over 10 years, and absolutely no answers to what was wrong.’
John was eventually diagnosed with a rare genetic disease called CANVAS (which affects the brain). ‘It was reassuring to finally confirm my diagnosis genetically, and it’s exciting to know that, in the near future, others with these types of conditions will be able to get a diagnosis quicker than I did,’ he said.
Study co-author Dr Kishore Kumar added: ‘For patients like John, the new test will be a game-changer, helping to end what can be a taxing diagnostic odyssey.’
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.
Dr Kumar said 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. 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. This diagnostic odyssey can be quite stressful for patients and their families.
‘This new test will completely revolutionise how we diagnose these diseases. 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.’
Although repeat expansion disorders cannot be cured, 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 test works by scanning a patient’s genome using technology called Nanopore sequencing.
Dr Deveson explained: ‘We’ve programmed the Nanopore device to hone in on the roughly 40 genes known to be involved in these disorders and 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 a patient’s genes, which are the hallmarks of disease.
‘In 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 Nanopore technology used in the test is smaller and cheaper than standard tests, which the team hopes will ‘smooth its uptake into pathology labs’.
Dr Deveson said: ‘With Nanopore, the gene sequencing device has been reduced from the size of a fridge to the size of a stapler, and costs around $1,000 compared with hundreds of thousands needed for mainstream DNA sequencing technologies.’
Fellow co-author Dr Gina Ravenscroft said once the method gains clinical accreditation, the test will also transform research into genetic diseases.
She commented: ‘Adult-onset genetic disorders haven’t received as much research attention as those that appear early in life.
‘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.’ AMP
