Research Report 2008

Ever tried searching for a needle in a field of haystacks?

Why are so many young men around the world dropping dead? Dr. Terry-Lynn Young and a team of researchers from several disciplines here at Memorial threw themselves into finding that answer. First they found the genetic link on a particular chromosome. That wasn’t enough. They had to find the exact gene.

It wasn’t like finding a needle in a haystack — it was like finding a needle in a field of haystacks.

On Feb. 28, 2008, this tenacious team revealed that they found the arrhythmogenic right ventricular cardiomyopathy gene. ARVC can be treated. People carrying the gene can now be identified using a molecular test and implanted with a fast-acting defibrillator. And when entire families need to be tested, knowing who carries the gene is a huge part of the battle. Genetic disease research is a priority at Memorial which means our researchers are not only solving medical mysteries — they’re saving lives.

Dr. Terry Lynn Young

Men in families affected by ARVC,which is highly prevalent in Newfoundland and Labrador, 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 the interdisciplinary research team in cardiac genetics from Memorial University, led by Drs. 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 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.”

Over several years the team has used the knowledge of the gene’s location on chromosome 3 to identify carriers of the lethal mutation. As a result of this discovery, doctors are already performing life-saving interventions to those with this deadly condition. Defibrillators have been implanted in adult carriers and on development of ventricular fibrillation (the event causing sudden death) a shock is 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.”

Copyright © 2008 Memorial University of Newfoundland