Researchers at Memorial University have discovered the gene responsible for ARVC (arrhythmogenic right ventricular cardiomyopathy), a deadly genetic heart condition highly prevalent in Newfoundland and Labrador. As a result of this discovery, doctors are already performing life-saving interventions to those with this deadly condition. 

Men in affected families often die at a young age. In fact, according to genetic counselor Kathy Hodgkinson, “clinical information collected from affected families indicates that only half of male carriers survived to 41 years of age.”  But now, an interdisciplinary research team in cardiac genetics from Memorial, led by Drs. Terry-Lynn Young, molecular geneticist; Patrick Parfrey, clinical epidemiologist; and Sean Connors, cardiologist; has identified the genetic cause of the disease. This discovery, published in the Feb. 28 online American Journal of Human Genetics (co-first authors Nancy Merner and Kathy Hodgkinson), could lead to more interventions and, eventually, a cure for this deadly disease.

“Before now, the location of the gene associated with the disease was known to be on a specific but rather large region of chromosome 3,” said Dr. Young. “We sequenced the 20 genes in this critical disease region, and found a mutation in a novel gene (entitled TMEM43) in all clinically affected family members. The gene codes for a protein in the membrane of the cardiac cell, but its function is currently unknown.” As a result of this discovery researchers will further investigate this gene for other forms of heart disease. 

Over several years the team has used the knowledge of the gene’s location on chromosome 3 to identify carriers of the lethal mutation. Defibrillators have been implanted in adult carriers and on development of ventricular fibrillation (the event causing sudden death) a shock has been delivered to the patient’s heart, thus reversing the ventricular fibrillation. “We have inserted nearly 100 defibrillators in mutation carriers, and clearly demonstrated that lives were saved,” reported Dr. Connors. “In fact survival after defibrillator implantation was excellent compared to those who did not receive a defibrillator.”

At a news conference and public announcement about the gene discovery, held Feb. 28, two members of affected families told their stories. Rosalie Cater had a defibrillator implanted six years ago after a heart incident. She carries the gene and one of her sons is also affected; he has a defibrillator and it has already gone off once, saving his life. Vicky Connolly comes from another ARVC family, but she now knows that she does not carry the gene.

Dr. Parfrey said he is so proud that the work on identifying the ARVC gene was all done in Newfoundland through the hard work of multidisciplinary teams. “This is a model for future genetic work.”

The strategic plan for clinical research at Memorial University and Eastern Health has identified genetic disease research as its priority, and has established an interdisciplinary research team in human genetics to ascertain families with genetic disease; to determine their genetic cause; to examine the ethical, economic, environmental, legal and social issues associated with the application of genetic tests in the community; and to determine the impact of genetic and clinical screening programs in the community. “The sudden cardiac death project is a successful example of research deriving from this approach in which genetic counselors, molecular geneticists, clinical epidemiologists, cardiologists, philosophers, and health policy experts have functioned as a team and coalesced around trying to solve a major clinical problem,” said Dr. Parfrey.

The sudden cardiac death research was funded by Genome Canada, the Canadian Institutes for Health Research, the Canadian Foundation for Innovation, the Janeway Hospital Foundation, the Government of Newfoundland and Labrador and St. Jude Medical. Collaborators included Dr. Ludwig Thierfelder at the Max-Delbruck-Centrum fur Molekulare Medizin in Berlin, Dr. William McKenna at the Heart Hospital in London, England, and Dr. Anne Bassett at the University of Toronto.