Unlocking genetic mysteries

When two siblings came to the Stollery Children’s Hospital with developmental delays and unusual facial features, doctors suspected a rare genetic disorder called Alazami Syndrome. Standard genetic tests weren’t able to confirm the diagnosis, so they turned to the Translational Genomics Hub (TGH) for help.

Supported with funding from the Stollery Children’s Hospital Foundation through the Women and Children’s Health Research Institute, the THG brings together experts from different areas of biology and genetics to solve genetic mysteries. The team evaluates the results of specialized genetic tests and runs experiments to confirm their findings.

Their goal: identifying new genetic disorders, or variants of existing ones, to provide a diagnosis.

“It offers an extra layer of possibilities — both for clinicians and researchers — to complete those complex genetic investigations,” says Oana Caluseriu, a clinical geneticist and associate professor in the Department of Medical Genetics.

She leads the TGH alongside Todd Alexander, a Foundation-funded researcher and chair of the Department of Pediatrics.

The mystery of the siblings — aged 9 and 17 — was solved by medical geneticist Saadet Andrews. She determined they have Alazami Syndrome from a gene variant that hadn’t yet been recorded in medical journals.

Andrews’ findings were published in June 2025, confirming her diagnosis for the family and updating the specific variant she found in a public database to help medical geneticists all over the world.

For those who’ve waited decades for answers, a genetic diagnosis comes as a relief, even if no treatment is available. It may allow families to access community supports for their loved ones or prevent the disorder from recurring in their family tree.

To date, about 7,000 genetic disorders have been clinically described globally, but not all have a gene attached or a cause identified. “There is still a lot of work to do, and all of us are just adding one little brick at a time,” Caluseriu says.

In the three years since it launched, the TGH has expanded the types of tests it offers. This is good news for those still waiting for answers — like the large family with whom Caluseriu has been working to identify a fatal, genetic disorder that has afflicted five generations. After identifying a promising gene, she used an online platform — “kind of a dating app for researchers” — that matched her with colleagues from around the world who have found the same gene in their patients. She connected with a research group in Australia and a scientist in Calgary, resulting in a rewarding collaboration.

“It has taken years and a lot of effort, but we are now getting ready to write the manuscript and describe a new genetic disorder,” she says.“It’s a very complex process, but once we convincingly demonstrate our findings, we will be able to work with the family to avoid the devastating outcomes that have ravaged so many lives. And the same will happen for any other family carrying the same faulty gene anywhere in the world who accesses a genetic service.”