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The cerebral cortex is the region of the brain closely associated with information processing, attention, awareness and conscious thought.  This wavy outer layer, only a few millimetres thick, is the human brain’s most prominent feature. Without it we’d lose our ability to think, process sensations and communicate via language.

Scientists Dr. Guang Yang, PhD, Dr. Mike Innes, MD, and Dr. Quan Long, PhD, members of the (ACHRI) at the Cumming School of Medicine (CSM), have discovered a rare condition that causes malformations of the cerebral cortex. They collaborated with an international team including scientists at Harvard University, Exeter Genomics Lab in the UK, and Hopital d'Enfants in France. The research is published in .

Working in mice, the team found that variants in the protein CELF2 upset the differentiation of specific kinds of brain cells — a mutation associated with abnormal growth and erratic cortical folding in humans. This is important, because the precise folding of the cortex creates a large surface area necessary for its normal function.

"The development of the cortex is a delicate process, and we can see that any variation can have significant outcomes in children,” adds Yang, who holds the Canada Research Chair in Regulatory Genomics.

The team went on to identify and contact, through an international gene platform, families with the CELF2 protein variant to better understand their children’s outcomes. All of the children in the study had similar developmental disorders with some speech and language impairment. In each of the cases, magnetic resonance imaging (MRI) showed poorly formed cortex patterning in the bitemporal and bifrontal cortical areas.

In addition to identifying the rare condition and its effect on the cortex, the researchers found that CELF2 binds to a specific set of messenger RNAs that when dysregulated are known to cause developmental disorders such as autism spectrum disorder (ASD), speech delay and intellectual disability.

“We are learning from families how a small change at the genetic level can result in a cascade of biological changes that result in learning challenges for these children,” says Innes, a clinical geneticist at Alberta Children’s Hospital. “This connection brings us one step closer to improved diagnostic screening which will allow us to identify more affected children and find possible treatments.”