Childhood blindness: long haul collaboration leads to major discovery

Montreal, September 8, 2022 – The discovery of genes associated with childhood blindness is of immediate and significant benefit to people with vision loss and those around them. An essential step to confirm the clinical diagnosis, establishing a genetic cause opens the door to targeted and personalized therapeutic avenues.

A discovery published today in the journal Science Advances shows that mutations in the gene BCOR cause early-onset retinitis pigmentosa (RP), a group of rare eye diseases that cause progressive vision loss.

Conducted by postdoctoral fellow Dr. Maéva Langouët and research professional Christine Jolicoeur in the laboratory of Dr. Michel Cayouette, at the Montreal Clinical Research Institute (IRCM) and Professor, Department of Medicine at University of Montréal, in close collaboration with Dr. Robert K. Koenekoop, director of Pediatric Ophthalmology at the Montreal Children’s Hospital and a team of international collaborators, this research work provides exciting prospects for the advancement of science and patient care.

"Helping Quebec families with vision loss, identifying their causal gene, and developing safe treatments to slow or stop retinal degeneration or even improve visual function are my career goals," says Dr. Koenekoop, who is also Senior Scientist in the Child Health and Human Development Program at the Research Institute of the McGill University Health Centre. “So when we found mutations in BCOR, a “cancer gene” involved in the development of B-cell lymphoma and other cancers, in a Quebec family with three boys who had vision loss, but no cancer, we knew that we had found something that needed further investigation.”

Dr. Koenekoop instantly thought of inviting Dr. Cayouette, who is internationally recognized for his work on the biology of the retina - the thin layer of nervous tissue at the back of the eye that is critical for vision - to join him in this project.

“Through a close collaboration with Dr. Koenekoop and thanks to a dedicated Quebec family, we were able to discover exactly how the identified mutations in BCOR cause vision loss,” adds Dr. Cayouette. “Similar to a thermostat regulating the temperature in a house, we discovered that BCOR precisely regulates the level of expression of many retinal genes. When genetic errors appear in BCOR, this regulation process is altered, leading to abnormal activity that eventually cause retinal cell death and vision loss.” 

In addition to providing a potential path to gene therapy, this work suggests that manipulating BCOR may alleviate or diminish the harmful actions of other gene mutations leading to RP.

“Identifying new genetic causes of inherited eye diseases offers immediate and significant benefit to the individuals being diagnosed as well as those around them. This can strengthen or confirm a clinical diagnosis, provide more information about the potential progression of the disease and opens the door to targeted and personalized therapies,” says Fighting Blindness Canada (FBC). FBC is proud to have provided funding towards this discovery.

A long path toward this discovery

Several developments make this research work unusual and worthwhile. While a new gene discovery usually takes from six to 12 months, the uncovering of the BCOR mutations took much longer. Funded in part by the Canadian Institutes of Health Research, Fighting Blindness Canada, the Institut de Recherches Cliniques de Montréal (IRCM) and the Montreal Children’s Hospital Foundation, the research required more than five years of work by a team of dedicated scientists and clinicians.

More than 200 genes involved in retinal degeneration have been identified, but about 40 to 50 percent of cases are still a mystery.