News | Thursday, 13th June 2019
Breakthrough DNA study on congenital heart condition wins award
Dr Donna Page collects British Cardiovascular Society's Young Investigator of the Year Award
A lecturer has won a prestigious prize for breakthrough DNA research that uncovered two genes associated with the most common severe congenital heart condition.
Dr Donna Page, Lecturer in Life Sciences at Manchester Metropolitan University, collected the British Cardiovascular Society (BCS) Young Investigator of the Year Award as part of a combined British Cardiovascular Society, British Atherosclerosis Society and British Society for Cardiovascular Research (BCS/BAS/BSCR) competition.
She won the award for her post-doctoral investigation, funded by the British Heart Foundation and published in the Circulation Research journal, into the DNA of people with Tetralogy of Fallot (TOF), a combination of four specific heart defects present at birth.
For the first time, we identified two genes, NOTCH1 and FLT4, that contribute to the development of the condition in a significant proportion of patients
Proud of prestigious award
Dr Page said: "I’m really proud and honoured to receive such a prestigious award and hope it will help with funding applications for further research into the causes of TOF and other congenital heart diseases."
The award recognises the work of young researchers and it is a competitive field – the other three finalists were from the University of Oxford.
Dr Page and her colleagues used a large group of patients with the condition and carried out a technique known as whole exome sequencing whereby they map all of the protein-coding regions in each of a person’s complete set of genes.
Dr Page explained: "We sequenced the DNA of 829 individuals with TOF and assessed the incidence of any unique mutations that are predicted to cause harm or damage.
"We then used a number of control exomes and a big database of 140,000 DNA sequences of individuals who don’t have a congenital heart disease in order to make a comparison.
"For the first time, we identified two genes, NOTCH1 and FLT4, that contribute to the development of the condition in a significant proportion of patients.
"We found that 7% of our TOF patient cohort had a unique, harm-causing mutation in either NOTCH1 or FLT4. This is the biggest genetic contribution to TOF identified to date."
Our findings are a good foundation and set a precedent for the identification of further genes contributing to TOF in larger studies
Cause of TOF largely unknown
Around 1% of babies are born with a congenital heart condition and in between 8% and 10% of those cases the condition will be TOF, making it the most common severe congenital heart condition.
One of the four specific defects of TOF is a hole between the two chambers of the heart, meaning oxygenated and non-oxygenated blood mixes, and requires open-heart surgery near enough straight after birth to remedy it in the majority of cases.
It is estimated about one in every 3,000 people in the UK have TOF, the causes of which is largely unknown.
As adults, TOF sufferers can develop more complications and symptoms such as an irregular heartbeat or an expansion of the right chamber, requiring valve replacement surgery in some instances.
Dr Page said the identification of two of the largest contributing genes to TOF is the start of a long journey into improving what little knowledge we have about the causes of the condition.
She said: "Some TOF patients may ask if their children will have the condition and due to our current lack of understanding, we are not able to say for sure.
"It’s about trying to understand why people are being born with these congenital conditions. Every patient’s disease can be caused by a different mutation; it is a very complex disease.
"Our findings are a good foundation and set a precedent for the identification of further genes contributing to TOF in larger studies."
The four specific heart defects in Tetralogy of Fallot are:
- a hole in the wall dividing the left and right ventricles of the heart, the heart’s large chambers (ventricular septal defect)
- the aorta – the largest artery – is positioned directly over a ventricular wall defect instead of over the left ventricle (overriding aorta)
- a blockage or obstruction in either the right or left ventricular passage from which bloods flows out (pulmonary outflow tract obstruction)
- thickening of the walls in the right ventricle of the heart (consequent right ventricular hypertrophy)
