New genetic discovery helps restore mobility in children with rare neuromuscular disease

A new genetic discovery has changed the lives of two Australian siblings with neuromuscular disease, helping to give them the ability to walk again.

The genetic research, led by Sydney Children’s Hospitals Network and University of Sydney’s Prof Sandra Cooper, identified a new genetic testing mechanism that enabled doctors to pinpoint the exact gene causing the sibling’s rare disease and subsequently, treat their condition with existing medicine, ‘ventolin’.

The treatment has successfully restored the sibling’s mobility, giving them back the ability to stand, walk and now, drive.

“I don’t even know the right words; that would be an understatement. I can get out of my wheelchair and I can do everything independently. I can drive myself to work, stay at a mate’s house, use their bathroom – all these problems that I once had, these barricades, they are just gone now,” said one of the treated siblings, who wished to remain unidentified.

The discovery of the new mechanism was a collaborative effort between Prof Cooper, her team at Kids Neuroscience Centre (KNC) (Kids Research) and colleagues at Max Planck (Göttingen) and means researchers can now test for genetic errors in the non-coding part of a gene, mistakes that were previously undetectable.

“Once we knew that this gene was the culprit in this family, it was already known that individuals with genetic defects in this particular gene are known to improve with salbutamol treatment (ventolin), a common asthma medication that is safe and readily tolerated,” said Prof Cooper, Joint Head of Kids Neuroscience Centre.

“With this information, Dr Roula Ghaoui (a neurologist in KNC) was able to immediately implement precision treatment for this family.”

“This heroes the inter-disciplinary strengths of research across our Sydney Children’s Hospitals Network, and our unique ability to bring new research discoveries and innovations so quickly into a clinical reality for families.”

Humans have 20,000 protein coding genes - and for many neurological conditions, defects in any one of 100 genes can cause a similar clinical presentation.

“It is really difficult to find the genetic mistake causing an inherited disorder because you can’t just input a DNA sequence and come out with an explanation,” she said

“We all have approximately 10,000 changes in our DNA that differ to the reference human genome; this is natural genetic variation.

"Finding the DNA mistake at the root cause of an individual’s inherited disorder can be like finding a needle in a haystack.”

“But now, in defining this new mechanism, we will have the ability to diagnose families with different genetic conditions around the world, including neurological, cardiac, metabolic and hereditary cancer and offer precision medicine to directly treat their condition.”

The new genetic mechanism has since identified a further 24 families who live with the same class of genetic variant.

Approximately 50 per cent of children admitted to paediatric hospitals have an underlying inherited condition. These inherited disorders, though individually rare, are collectively the most common cause of severe disability in childhood.

“The ability to obtain a precise genetic diagnosis is a key step for every family affected by a rare inherited disorder as it not only allows them to be eligible for clinical trials and receive personalised medical care but also enable family planning,” Prof Cooper said.

“It has the potential to be life-changing.”

The research, titled ‘Pathogenic abnormal splicing due to intronic deletions that induce biophysical space constraint for spliceosome assembly,’ has been published in The American Journal of Human Genetics (AJHG).

For the full published study, please visit: Pathogenic Abnormal Splicing due to Intronic Deletions that Induce Biophysical Space Constraint for Spliceosome Assembly.