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 Stocker 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.
CFRI Link: www.cfri.ca/news/news/2015/06/16/newly-discovered-genetic-mutation-ends-a-young-girl-s-diagnostic-odyssey
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.
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 Vallance, Dr. 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.
Mining for Miracles, the BC mining community's longstanding fundraising campaign for BC Children's Hospital, raised more than $1,066,184 on May 7 at its signature event, the Teck Celebrity Pie Throw. Participants raised funds by volunteering to take a pie in the face while asking friends, family and colleagues to pledge their support.
This year, representatives from Teck, Goldcorp, New Gold, Golder Associates, Amec Foster Wheeler, BLG, McMillan, Hatch, Finning, Ausenco, AME BC and MABC participated in Pie Throw. B.C. Energy and Mines Minister Bill Bennett also got into the act, challenging the audience at Pie Throw to raise $10,000 to “pie a politician”. The industry happily obliged, raising the $10,000 so that Minister Bennett could receive a pie in support of BC kids.
“The Teck Celebrity Pie Throw always attracts a lot of interest and a big crowd, and this great participation ultimately has a huge impact on the care children receive at BC Children’s Hospital,” said Teri Nicholas, president and CEO of BC Children’s Hospital Foundation.
“The B.C. mining sector has a proud tradition of giving back to communities and I’d like to congratulate all the participants, volunteers and donors from across the industry for raising these funds in support of child health in B.C.,” said Bill Bennett, Minister of Energy and Mines.
“Supporting BC Children’s Hospital is part of the B.C. mining industry’s long history of working to strengthen communities across the province,” said Jason Weber, co-chair, Mining for Miracles.
“Eighteen representatives from across the industry participated in Pie Throw and soundly beat the $600,000 fundraising goal which is a testament to their commitment and the generosity of the entire mining industry,” said Jeff Hanman, co-chair, Mining for Miracles.
The Pie Throw also featured the 2015 Diamond Draw benefiting BC Children's Hospital. The winner received a diamond package, valued at over $16,000, including a 1.20-carat cushion-cut diamond, gold and a designer setting donated by C3 Alliance Corp., Teck and Costen Catbalue.
The Pie Throw and Diamond Draw were supported by hundreds of mining, exploration, development companies, service providers and suppliers across BC, Alberta, the Yukon and Northwest Territories, and their employees, family and friends.
Funds raised by Mining for Miracles in 2015 and 2016 will support the development of the CAUSES Clinic at BC Children’s Hospital. The new CAUSES Clinic will provide diagnostic DNA testing to support the accurate and efficient diagnosis of rare genetic diseases in children who would otherwise require numerous tests or who might not be diagnosed at all. The clinic will also provide families with genetic counselling, clinical interpretation of complex testing results, and personalized recommendations for treatment.
The CAUSES Clinic’s single test will reduce the number of invasive tests required, such as biopsies, biochemical tests, expensive single gene tests or MRI scans, which may even require sedation. There are 7,000 known genetic disorders and the CAUSES Clinic will use a single genomic test capable of identifying all of these at once. This may reduce the number of tests required to diagnose a patient’s condition from 10 or more to just one. This has the potential to reduce costs to families and the health-care system.
The partnership between BC Children’s Hospital Foundation and Mining for Miracles is a leading example of how industry, institutions and social-profit organizations can work together to provide world-class health care and services to the children and families of BC. Please visit www.miningformiracles.ca for more information and to donate.