Researchers in the U.K. have identified a new gene linked to the development of congenital heart disease (CHD) among newborn babies through large-scale sequencing analysis.

The finding will help experts improve their understanding of this most common type of birth defect.

The study, published in Nature Genetics, was led by Professor Bernard Keavney, from The University of Manchester and Newcastle University and included researchers from various other UK universities.

Congenital heart disease is one of the most common defects in the structure of the heart, around 7 in 1000 people are born with the disorder – it is one of the main causes of childhood death. CHD is a general term for a series of faults in the structure of the heart and major blood vessels that is present from birth. With congenital heart disease there is something wrong with the structure of the heart; the cycle of pumping blood passed the lungs and supplying oxygen-rich blood to cells and tissues throughout the body is faulty.

Antenatal screening of CHD is conducted with fetal echocardiography – a kind of ultrasound scanner. Postnatal diagnosis is made rapidly by identifying hallmark signs of cyanotic heart disease – bluish coloring of the skin.

Only by properly identifying the genes responsible for the CHD can patients who survive into adulthood receive really effective treatment.

Around 20% of CHD cases occur as a result of a predisposing cause, such as Down’s Syndrome. However, scientists are not really sure what the genetic causes of the remaining 80% of cases are.

Just in case

In this study, a total of 2,000 patients with CHD were analyzed. The researchers measured more than half a million genetic markers using state-of-the-art sequencing and genome mapping techniques, and compared the genetic markers of the CHD patients to 5,600 healthy people (the control group).

The team identified a link between one region of the human genome and a risk of developing atrial septal defect (ASD) – essentially a hole which allows blood to leak between two compartments of the heart – normally a septum blocks this from happening.

Identifying the gene responsible for a type of CHD is a major medical breakthrough, the authors explained. BHF Professor Keavney, Director of the Institute of Cardiovascular Sciences at The University of Manchester, said: “We found that a common genetic variation near a gene called Msx1 was strongly associated with the risk of a particular type of CHD called atrial septal defect or hole in the heart.”

He added:

“ASD is one of the most common forms of congenital heart disease, and it carries a risk of heart failure and stroke. We estimated that around 10% of ASDs may be due to the gene we found. We can now work to find out how Msx1 and/or its neighbour genes affect the risk of ASD.”

The team examined all types of CHD, however, they weren’t able to identify a common marker in every type.

Professor Keavney said that a larger study would be able to identify more genes that cause other types of CHD. This would benefit high risk families, who would be offered genetic counseling. Eventually, doctors might even be able to prevent congenital heart disease from developing during the early stages of heart formation.

Keavney added that “when we identify genes important in the development of the heart because they have gone wrong, it helps us understand normal development better. Such an understanding is fundamental to any attempt to treat people with heart disease at any age – for example those suffering from heart failure – using regenerative medicine.”

Dr Shannon Amoils, Senior Research Advisor at the BHF, which part-funded the study, concluded that although we’ve made huge advances in medicine that allow babies born with heart disease to survive at rates considerably higher than when the BHF was founded in the 1960s, “we still need to fund much more research like this, to better understand the fundamental causes of congenital heart defects.”

Dr. Amoils said:

“These important results show how large collaborative studies are incredibly useful for uncovering the influence of our genes on congenital heart disease.

As researchers continue to identify other associated genes, we will be able to better predict the chances of children being born with heart problems, and will also learn more about the underlying processes that can go wrong in the developing heart.”

A few months ago, scientists at the Gladstone Institutes identified a finely tuned mechanism by which fetal heart muscle develops into a healthy and fully formed beating heart, which offered new insight into the genetic causes of CHD.

Published in the journal Nature Genetics, the researchers described the roles that two genes – Ezh2 and Six1 – play in embryonic heart development – and how they are related to the development of CHD.

Stem cell therapy offers some hope for children with CHD. For a long time scientists have been waiting for when a damaged heart could be rebuilt or repaired by using the patient’s own heart cells.

Scientists explained in the journal Circulation that heart stem cells from children with congenital heart disease were able to rebuild the damaged heart in the laboratory.

Written by Joseph Nordqvist