Researchers at the Garvan Institute of Medical Research have developed a single test for over 50 genetic diseases that will cut diagnosis time from decades to days. Garvan researchers have shown how new genomic sequencing technology can reduce the 'diagnostic odyssey' experienced by people with rare neurological and neuromuscular diseases.
A single DNA test has been developed that 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 new test avoids a ‘diagnostic odyssey’ for patients that can take decades.
The team, from Australia, UK and Israel, has shown, published in Science Advances that the test is accurate. They are now working on validations to make it available in pathology labs.
They expect it to be standard in global pathology labs within five years.
‘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 Dr. Deveson.
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,’ he says. ‘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,’ says Dr. Deveson.
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’ says Dr Deveson.
The team expects to see their new technology used in diagnostic practice within the next two to five 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, says Dr Gina Ravenscroft, a co-author of the study and a researcher working on rare disease genetics at 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,’ she says. ‘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.’
