A Single Genetic Test Can Accurately Diagnose 25 Rare Diseases Faster Than Ever

Scientists have developed a quick genetic test that can diagnose a large range of rare muscle and nerve diseases with near perfect accuracy.

Tandem repeat disorders are a family of over 50 inherited diseases, including Huntington’s disease and amyotrophic lateral sclerosis (ALS), that seem to occur when short DNA sequences are repeated too many times.


Tandem repeats can arise through errors in DNA replication, which are then passed down to subsequent generations. Many are benign, however, and all living things have them in different patterns and combinations – making them a useful tool for determining relationships between individuals, like parentage or tracing the origins of infections.

But sometimes they arise in problematic parts of our genomes.

Depending on where they occur, unusually long forms of these repeating sequences can drive neurological or neuromuscular degeneration. Yet because there are 37 known genes that are linked to short tandem repeat disorders, it can take multiple tests before identifying the ones responsible for an individual’s symptoms.

For patients like John – one of the participants involved in a new study – it can take over a decade to whittle down the options.

John was ultimately diagnosed with cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, or CANVAS for short. This is a neurodegenerative movement disorder, which is linked to an expansion of repeat DNA sequences in the gene RFC1.

Just in this one gene, however, there are a diversity of ways short DNA sequences can be repeated, which makes a blanket diagnostic test difficult.


“I had test after test for over 10 years and absolutely no answers as to what was wrong,’ says John.

Neurologist Kishore Kumar says he and his colleagues at the Garvan Institute for Medical Research in Australia refer to this stressful process as the ‘diagnostic odyssey’. As patients like John wait years and years for answers, their symptoms grow gradually worse.

While there’s currently no cure for tandem repeat disorders, early diagnosis can help patients manage their symptoms, and hopefully stall some of the disease progression, so the newly developed test should make a big difference to patients.

“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,” says Kumar, “helping patients avoid years of unnecessary muscle or nerve biopsies for diseases they don’t have, or risky treatments that suppress their immune system.”

The newly developed assessment is based on nanopore technology, which can analyze long DNA or RNA fragments in known repetitive regions of the human genome.


Taking a single DNA sample from an individual’s blood, researchers can pass the nucleic acids through a protein nanopore, using changes in electrical current arising from the molecular interactions to decode in real time the sequences from 40 genes known to be connected to 25 tandem repeat diseases.

Among 37 patients who were tested using this method, including John, all were correctly matched to their neurogenetic disease.

“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 genomicist Ira Deveson, also from the Garvan Institute.

Current gene sequencing tests require machines as large as fridges, whereas the nanopore technology is no bigger than a stapler. It also costs hundreds of thousands of dollars less, meaning it could be easily scaled up and distributed.

Researchers are now trying to get the method clinically approved. They hope in two to five years the diagnostic test will be used regularly.

The study was published in Science Advances.