A cardiologist from the Peter Munk Cardiac Centre at the Toronto General Hospital finds evidence that only one of the 21 genes normally associated with Brugada Syndrome is a definitive cause of the condition.
Brugada syndrome is a genetic condition that causes abnormal electrical activity within the heart that increases the risk of sudden cardiac death. It tends to be genetically related with the abnormal heart rhythm often occurring when a person is resting.
“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 evaluations 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.
“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.”
Researchers have found that only the SCN5A gene, originally discovered 20 years ago for Brugada Syndrome, was 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.”
“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,” says Jonathan Berg, MD, PhD, FACMG whose group leads the ClinGen Cardiovascular Genomics Clinical Domain Work Group under which this Expert Panel completed their work on determining which genes are actually associated with Brugada Syndrome.
The Peter Munk Cardiac Centre opened in 1997 and has saved countless lives working on over 55,000 patients a year. It is based in at the Toronto General Hospital and the Toronto Western Hospital.