CFRI researchers and their collaborators have discovered a new genetic mutation in a six-year-old-girl. Their finding solved a medical mystery for the young girl and her family. She was being treated at BC Children’s Hospital for developmental delays and other serious health problems that doctors were unable to explain. The medical team’s recently published findings may provide answers and eventually lead to improved therapies for other children who have similar symptoms and don’t respond to current treatments.

On May 22, 2015, CFRI investigators Dr. Sylvia Stockler and Dr. Elizabeth Conibear, along with collaborator Dr. Silvia Corvera, a professor at the University of Massachusetts Medical School, presented their discovery to an audience of leading researchers who study genetic disorders.

These researchers had gathered to attend the Garrod Symposium, an international event for scientists held in Vancouver, BC. The girl’s family also participated in the Symposium to speak about how this research has impacted their lives.

Dr. Clara van Karnebeek, a CFRI Investigator and member of the study team, chaired this year’s Garrod Symposium.

Q&A with Dr. Sylvia Stockler

CFRI Clinical investigator; Professor and Head of the Division of Biochemical Diseases, UBC Department of Pediatrics; Program Director, Biochemical Diseases, BC Children’s Hospital.

The genetic discovery was recently published in the scientific journal Orphanet Journal of Rare Diseases. Dr. Stockler, co-lead author of the publication, talked about this discovery and what it means for children.

What did you discover?

We discovered a new mutation in a gene that codes for a protein called Rabenosyn-5 (Rbsn-5) by testing a portion of the patient’s genetic material.

The patient is a six-year-old girl who has developmental delay, intractable seizures, and various physical abnormalities. Doctors found abnormal levels of certain chemicals in the girl’s blood and urine, which suggested she had an underlying metabolic disorder, but her symptoms didn’t fit any known condition. 

Finding this mutation finally provided a diagnosis that explains the young girl’s symptoms. With more research, we may ultimately be able to add Rbsn-5 deficiency to the list of treatable genetic conditions.

How does the mutation you discovered cause health problems?

Rbsn-5 plays a critical role in endocytosis, a vitally important process by which cells absorb nutritional substances, hormones, vitamins and other materials they need to function properly. Disruptions to endocytosis cause problems in other basic cellular processes, leading to the severe, multi-organ disorder observed in this patient. 

How will this discovery improve care for children in BC and beyond?

This is the first known mutation affecting Rbsn-5 in humans, but it’s very likely there are other patients who have developmental delays and severe epilepsy because of the same genetic defect. Identifying other patients with this mutation will bring peace of mind to their families, who may have spent years seeking a diagnosis. 

Once we find other individuals with Rbsn-5 deficiency, we’ll also be able to identify targets for treatment, which may lead to new therapies. We’re able to treat similar metabolic disorders through special diets, supplements and drugs. 

What are the next steps?

We’re currently trying to find other children who have the same genetic mutation as the girl in this study. Genetic material is needed from multiple patients in order to develop a reliable screening test for this disorder. That’s why we’re excited that the advanced techniques used in this study will soon be more widely available through a new research program involving CFRI researchers at BC Children’s Hospital called ‘CAUSES’.

CAUSES will provide ‘genome-wide sequencing’ – a scan of all 2,200 genes – to 500 children over three years to help diagnose rare, unexplained medical conditions. The study will also offer genetic counselling and personalized recommendations for treatment to families. It is hoped the research will help develop an evidence base to support the use of genome-wide sequencing within standard care for all kids in BC who need it.

We are optimistic that CAUSES will further our knowledge of Rbsn-5 deficiency, as well as other rare disorders, and contribute to more effective treatments that help children lead fuller, healthier lives.

Read more

Sylvia Stockler, et al, “Single point mutation in Rabenosyn-5 in a female with intractable seizures and evidence of defective endocytotic trafficking,” in Orphanet Journal of Rare Diseases, September 20, 2014.

Dr. Stockler is Professor and Head of the Division of Biochemical Diseases in the Department of Pediatrics at the University of British Columbia and Program Director, Biochemical Diseases at BC Children’s Hospital.

Study co-authors include CFRI researchers, Dr. Clara van Karnebeek Dr. Elizabeth Conibear, Dr. Ekaterina Nosova, Dr. Colin Ross, Dr. Kathryn Selby, Dr. Hilary VallanceDr. Margot van Allen , Dr. Wyeth Wasserman; Caspar Shyr, a UBC Doctoral Student; and Dr. Nicholas Au, a Clinical Assistant Professor of Pathology and Laboratory Medicine at UBC.


This gene discovery was part of the TIDEX gene discovery study lead by Dr. Clara van Karnebeek at CFRI and BC Children's Hospital. This research was supported by funding from BC Children's Hospital Foundation, the British Columbia Clinical Genomics Network, the Rare Diseases Foundation, Genome BC, the British Columbia Clinical Genomics Network, Canadian Institutes of Health Research, and National Institutes of Health.