University of Otago – Ōtākou Whakaihu Waka has led international research uncovering a new genetic cause for a rare developmental disorder that profoundly impacts brain growth and function in children.
The findings, recently published in the prestigious American Journal of Human Genetics, pinpoint specific changes in a gene called CRNKL1.
Co-author Associate Professor Louise Bicknell, from the Rare Disorder Genetics Laboratory in Otago's Department of Biochemistry, says this discovery sheds new light on the incredibly complex process by which our bodies create the "instruction manuals" essential for building and maintaining our brains.
Associate Professor Louise Bicknell
"Our bodies rely on a precise process called 'splicing' to read and process genetic instructions from our DNA and help generate the building blocks required in our body.
"While it's known that problems with the machinery that coordinates splicing can cause various genetic disorders, this new finding adds to a small but growing recognition of the potential severe impact on brain development in particular."
The research team studied 10 families impacted by a severe genetic disorder that results in affected individuals having profound pre- and post-natal microcephaly (smaller head circumference), with pontocerebellar hypoplasia (underdevelopment in brain stem and cerebellum), seizures and severe intellectual disability.
"Our journey to this discovery began here in New Zealand, through trying to help New Zealand families get answers for genetic disorders affecting their children," Associate Professor Bicknell says.
"Then, using our international connections, we were able to identify other families around the world, which was crucial for confirming our findings and understanding the full impact of these genetic changes."
In a striking discovery, nine of these families showed genetic changes in the exact same spot in the CRNKL1 gene.
All the affected children shared the same severe features, highlighting the strong link between these specific genetic changes and the disorder.
Lead author Dr Sankalita Ray Das, a Postdoctoral Fellow in the Rare Disorder Genetics Laboratory, says the research findings clearly show that CRNKL1 is crucial for healthy brain development.
"It also adds to a growing understanding that specific parts of the splicing machine have highly specialised roles, far more intricate than we previously thought."
This finding not only identifies a new genetic cause for a severe neurological disorder but also offers further clues into the complex ways our genes guide brain development, she says.
"Importantly, this knowledge has provided understanding for families affected by these severe conditions and lays the foundation for further research into why just the brain is affected by these genetic changes."
*The researchers received funding from the Neurological Foundation of New Zealand, Cure Kids and the University of Otago.
