Groundbreaking technology brings an end to John’s life-long diagnosis odyssey
Rare disorders may not individually affect many people. But collectively they impact about eight percent of Australians. Eighty percent of these rare disorders are genetic and disturbingly, as many as 70% of patients with these genetic diseases do not have a diagnosis. This leaves them in limbo, unable to access accurate information about their disease or potential treatments that might better manage their symptoms. It also prevents family members from making informed life choices, in the case of inherited disease.
John was one such patient. John was experiencing a debilitating loss of coordination and balance, which significantly impacted his quality of life. But no doctor or specialist could tell John why this was happening. And like many patients who spend months – or even years – searching for answers, this lack of diagnosis was the cause of great distress for John and his family. Without knowing the origin of his symptoms, John had no way of planning for the future or anticipating how his disease might develop.
The turning point in John’s diagnosis odyssey came when his genome was sequenced using breakthrough nanopore technology developed by Dr Ira Deveson, Head of Genomic Technologies at Garvan.
Garvan scientists have long known that there is a myriad of genetic diseases that are difficult to diagnose because they exist on DNA sequences that are too long to read. Prior to the development of Dr Ira Deveson’s nanopore technology, accurately diagnosing these genetic diseases – known as repeat expansion disorders – was extremely difficult. It required huge computers, months of processing and could only test for one disorder at a time, making it a slow and costly process.
To overcome these limitations, Dr Ira Deveson and his team have created a methodology to read previously unreadable sequences of DNA, opening up the possibility to diagnose many previously hidden genetic diseases. They built a nanopore long-read sequencing method that can analyse 50 tandem repeat expansion disorders across approximately 50 genes – all at the same time.
Nanopore technology has historically been seen as too error-prone and the process to get an accurate consensus of all the reads too slow and computationally intensive. To resolve this problem, Dr Deveson and his team of scientists, computer analysts and engineers developed a sophisticated methodology that effectively takes this process and miniaturises it. Where scientists previously needed a super-computer the size of a room to process the data, it can now be delivered on a handheld device, or even a smart phone. This makes it accurate, faster and more cost effective than other sequencing methods.
For John, this technology led to a diagnosis of cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). CANVAS was only recently discovered to be caused by an expansion in the RFC1 gene – one of the genes Dr Deveson’s work can now analyse.
For John, understanding the genetic cause of his symptoms helped him and his family make choices about what was important to them. It gave his children crucial knowledge about the possibility of an inherited condition that may affect their own life plans. It has also helped John access support, including a physiotherapist who specialises in neurological conditions and is working with him to manage his physical disabilities.
Importantly, John’s diagnosis may one day help connect him with clinical trials that are searching for ways to better manage his disease.
Dr Deveson’s groundbreaking technology opens up immense possibilities to help diagnose unsolved cases like John’s.
“There are so many applications,” Dr Deveson says. “It’s all DNA to us.”