A single blood test for more than 50 genetic diseases has been developed by scientists.
It cuts diagnosis of neurological and muscular disorders from decades to days. They range from epilepsy to motor neurone disease.
An international team hailed it as a ‘gamechanger’ and it could be in clinical use in two years.
Patients will get earlier therapy, undergo fewer surgical procedures and be protected against unnecessary side effects from drugs.
The illnesses are rare and often run in families – but do not present until adult life.
Co author Dr Kishore Kumar, of the Concord Hospital in Sydney, Australia, said: ‘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.
‘It will help patients avoid years of unnecessary muscle or nerve biopsies for diseases they don’t have, or risky treatments that suppress their immune system.’
The conditions are caused by unusually-long DNA sequences in genes – a phenomenon known as STR (Short Tandem Repeat).
Senior author Dr Ira Deveson, of the Garvan Institute, Sydney, said: ‘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.’
They can run in families – and are notoriously hard to diagnose. The new technique is quicker, cheaper and more accurate than current alternatives.
Dr Deveson said: ‘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.’
Study participant, named only as John, first realised something wrong when he experienced unusual problems balancing 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 ten years and absolutely no answers as to what was wrong.’
John was eventually diagnosed with a rare genetic disease called CANVAS, which affects the brain.
He said: ‘It was reassuring to finally confirm my diagnosis genetically. It is 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.’
They can be passed on through families, be life threatening and generally involve muscle and nerve damage, as well as other complications throughout the body.
Dr Kumar said: ‘For patients like John, the new test will be a game-changer, helping to end what can often be a taxing diagnostic odyssey.’
Current genetic testing for the illnesses – known collectively as ‘expansion disorders’ – can be ‘hit and miss.’
Dr Kumar said: ‘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 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.’
Repeat expansion disorders are incurable. But a quicker diagnosis can help doctors identify and treat complications sooner.
These include heart issues associated with Friedreich’s ataxia, a degenerative disease of the nervous system.
Using a single DNA sample, usually extracted from blood, the test works by scanning a patient’s genome using a method called Nanopore sequencing.
Dr Kumar explained: ‘We have programmed the 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.’
The machine is portable and inexpensive to run – promising smooth uptake into pathology labs.
Dr Deveson said: ‘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.
‘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 (£750) compared with hundreds of thousands needed for mainstream DNA sequencing technologies.’
The test described in the journal Science Advances is expected to be in doctors’ surgeries in two to five years. It will also transform research into genetic diseases.
Co author Dr Gina Ravenscroft, of the Harry Perkins Institute of Medical Research, Perth, said: ‘Adult-onset genetic disorders haven’t received as much research attention as those that appear in early life.
‘By finding more people with these rare adult-onset diseases, and those who may be pre-symptomatic, we will 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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