One whole genome in a cell contains at least 19 000 genes. A disease causing variant in a gene called CDH2 in a family with arrythmogenic right ventricular cardiomyopathy identified. Graph: SAMRC
Cape Town – In what has been hailed as the “biggest breakthrough in South African cardiology since Dr Chris Barnard’s first heart transplant” nearly 50 years ago, South African and Italian medical researchers have identified a gene that is a major cause of sudden death among young people and athletes.
“This discovery is a first in the world – on our soil – and will permit the diagnosis and possible targeted treatment of heart muscle disease in the future,” UCT Health Sciences faculty Dean Professor Bongani Mayosi said, adding it had taken 20 years for the breakthrough to be made.
“Today is a significant occasion in the history of science and the history of cardiology in this country. Heart disease is a major killer therefore, finding the origins of heart disease is a fundamental task of science,” he said.
The gene, called CDH2, causes arrhythmogenic right ventricle cardiomyopathy (ARVC), a genetic disorder that predisposes young people to cardiac arrest.
Notable cases of ARVC include Sevilla Football Club and Spanish international left wing Antonio Puerta who died from the condition, at the age of 22, in 2007. Puerta collapsed and lost consciousness on the field from cardiac arrest.
English professional footballer Matt Gadsby also died from the condition after collapsing on the pitch in 2006, aged 27.
According to estimates, sudden cardiac death claims the lives of more than five young South Africans a day. In Italy, about 50 000 people die suddenly every year.
In ARVC, the heart muscle tissue is replaced by fatty and fibrous tissue. This encourages the development of an abnormal heart rhythm such as rapid heart rhythm or rapid and erratic heart rhythm, that causes loss of consciousness and cardiac arrest. In the case of ventricular fibrillation, without a ready device to shock the heart, it causes sudden death in a few minutes.
PhD student Maryam Fish, who worked to find the gene, said the discovery was made through the study of two members of a South African family affected by ARVC. Through whole exome sequencing – a technique for speedy sequencing all of the expressed genes in a genome – the genetic mutation responsible for the disease in the family was narrowed down from more than 13 000 common genetic variants present in the subjects to 13 variations and then the discovery of the CDH2 gene.
The discovery of this gene has been validated by finding a second mutation on the same gene in another patient with ARVC belonging to a different family.
“(This) would allow us to identify members in families who may be carrying this disease and may be unaware of it. If we have a family member who we know has a mutation in this disease, we can have a look at the rest of their family, and if they are found to carry this mutation, they can be advised on behaviours to follow so they don’t develop the disease later in life,” Fish said.
This will make the early detection of many people affected by ARVC possible and see a reduction of cases of sudden death, Professor Peter Schwartz of the Italian Auxologico Institute of Milan said.
Often the diagnostic clinical signs of the disease become clear only after many years. If a subject with ARVC is a carrier of a mutation of the gene CDH2, it means that the subject is at a higher risk of cardiac disease, Schwartz said.
“Often people die and then the diagnosis is made. There are patients who have palpitations, who faint and the diagnosis is made and they are alive, but all too often the diagnosis is made afterwards.”
The mutation of the CDH2 gene is the indicator that a subject is genetically affected and allows the need to start preventive strategies such as lifestyle changes, Schwartz said.
South African Medical Research Council president and chief executive Professor Glenda Gray said: “This collaborative research is what we relentlessly seek to fund, because it directly translates into finding ways to save lives in South Africa.”
Cape Times/Iol News