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Toronto (July 5, 2018) – A new study published in Circulation, a peer-reviewed journal of the American Heart Association and led by a cardiologist at the Peter Munk Cardiac Centre at Toronto General Hospital has found evidence that only one of the 21 genes normally associated with Brugada Syndrome, a serious genetic heart condition associated with the risk of sudden arrhythmic death, is a definitive cause of the condition.
"The global impact of this important research is significant for scientists, medical professionals and patients who are genetically pre-disposed or who have been diagnosed with this potentially-fatal heart condition," says Dr. Barry Rubin, Medical Director, Peter Munk Cardiac Centre, University Health Network. "The evidence-based findings of our internationally-recognized, multi-disciplinary team of researchers could dramatically alter both the diagnostic and treatment pathway for patients with Brugada Syndrome as well as other genetic-based conditions."
The study's findings came as the result of evaulations conducted by the Clinical Genome Resource (ClinGen) expert panel led by Dr. Michael Gollob, cardiologist, Peter Munk Cardiac Centre and Chair, Peter Munk Centre of Excellence in Molecular Medicine. ClinGen is supported by the National Institutes of Health (NIH) in the United States.
"Our research examined the genetic evidence for 21 genes reported as single gene causes for Brugada Syndrome," says Dr. Gollob "Remarkably, 20 of 21 genes were classified as disputed evidence, indicating that genetic evidence to support causation of this disease by these specific genes was lacking," he says.
Researchers found that only the SCN5A gene, first discovered 20 years ago for Brugada Syndrome, was deemed a definitive cause of the condition. The study also highlights the risks associated with the genetic testing of genes that lack sufficient evidence for disease causation.
"Clinically, evaluating genes that lack validity for disease causality creates a risk of misinterpreting the relevance of genetic changes in these genes and may lead to inappropriate diagnostic conclusions and treatment in patients", says Dr. Gollob. "Our conclusions from this study are surely not unique to Brugada Syndrome. Invalid or questionable gene-disease associations are likely common for many diseases across multiple medical disciplines", he says.
"This ClinGen report highlights the importance and value of ClinGen's efforts to standardize and improve the databases used by laboratories to guide testing decisions and the interpretation of test results," said Jonathan Berg, MD, PhD, FACMG whose group leads theClinGen Cardiovascular Genomics Clinical Domain Work Group under which this Expert Panel completed their work on determining which genes are actually associated with Brugada Syndrome.
Based on their findings, the authors recommend that an evidence based evaluation of reported gene-disease associations should be completed prior to the testing of genes in patient care.
The Peter Munk Cardiac Centre is the premier cardiac centre in Canada. Since it opened in 1997, the Centre has saved and improved the lives of cardiac and vascular patients from around the world. Each year, more than 55,000 patients receive innovative and compassionate care from multidisciplinary teams in the Peter Munk Cardiac Centre, and the Centre trains more cardiologists, cardiovascular surgeons and vascular surgeons than any other hospital in Canada. The Centre is based at the Toronto General Hospital and the Toronto Western Hospital - members of University Health Network. www.petermunkcardiaccentre.ca
Phone: 416 340 4636