June 18, 2021

UCalgary scientists discover genetic condition linked to developmental disorders in children

Basic and clinical researchers team up to better understand rare diseases
Dr. Guang Yang and Dr. Mike Innes
Yang, left, and Innes reveal rare condition that causes malformations of the cerebral cortex. ACHRI

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 Alberta Children’s Hospital Research Institute (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 Cell Reports.

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.

MRI images of atypical cortical folding

Four young patients showing atypical cortical folding in MRI images.

"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.”


The researchers express their heartfelt thanks to the participating families. This research is supported by grants from the Canadian Institutes of Health Research, Azrieli Foundation, and the Alberta Children's Hospital Foundation. Dr. Mohamad-Reza Aghanoori, PhD, and graduate Shreeya Kedia have been supported by ACHRI fellowships.

Guang Yang is an assistant professor in the departments of Medical Genetics and Biochemistry & Molecular Biology and is a member of ACHRI at CSM.

Mike Innes is a professor in the departments of Medical Genetics and Paediatrics, a clinical geneticist at the Alberta Children’s Hospital, a member of ACHRI and the Hotchkiss Brain Institute at the CSM and is the national coordinator of Orphanet Canada.

Child Health and Wellness
The University of Calgary is driving science and innovation to transform the health and well-being of children and families. Led by the Alberta Children’s Hospital Research Institute, top scientists across the campus are partnering with Alberta Health Services, the Alberta Children’s Hospital Foundation, and our community to create a better future for children through research.