A new DNA test, developed by researchers at the Garvan Institute of Medical Research in Sydney and collaborators from Australia, the U.K., and Israel, has been shown to identify a range of hard-to-diagnose neurological and neuromuscular genetic diseases quicker and more accurately than existing tests.
“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,” says Dr. Ira Deveson, head of genomics technologies at the Garvan Institute and senior author of the study.
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,” says Deveson.
The study, published Friday in Science Advances, shows that the test is accurate, and allows the team to begin validations to make the test available in pathology services around the world.
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.
Current genetic testing for expansion disorders can be hit and miss, says Dr. Kishore Kumar. “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. We call this the ‘diagnostic odyssey,’ and it can be quite stressful for patients and their families,” he says.
“This new test will completely revolutionize 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,” says Kumar.
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 test works by scanning a patient’s genome using a technology called Nanopore sequencing.
“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,” Kumar says. “By unraveling 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,” says Deveson.