Major genetic discovery explains 10 percent of aortic valve disease

September 28, 2012, University of Montreal

Researchers at the Sainte-Justine University Hospital Center and University of Montreal have identified genetic origins in 10% of an important form of congenital heart diseases by studying the genetic variability within families.

"This is more than the sum of the genes found to date in all previous studies, which explained only 1% of the disease, says Dr. Marc-Phillip Hitz, lead author of the study published in , under the direction of Dr. Gregor Andelfinger, pediatric cardiologist and principal investigator leading an international research team, who calls this study "a very important step towards a molecular catalog, which ultimately may explain the evolution of disease in individual patients and allow to influence the progression of the disease."

Congenital heart malformations are at the forefront of all malformations in newborns, and one of the most important causes of infant mortality in . For their study, the researchers focused on malformations of the , where familial clustering of cases often suggests a hereditary component. The researchers therefore decided to adopt a "family approach" and selected families with several members having a heart condition, in order to be able to establish a direct link with the disease. Using very strict filtering criteria to identify possible causal –a structural form of variation of the that leads to an increase or decrease in the copy number of small parts of DNA within the genome– the researchers retained only rare variants directly involved in the disease processes and causing severe . The variants had to be carried by the patients but not by healthy members of their family. Researchers then validated the identified genes by confirming that they were highly expressed in the developing mouse heart.

The study also noted that many affected patients carried more than one rare variant. This finding had already been made in the context of other congenital diseases. In addition, the study reveals that in the 59 families analyzed, no copy number variants recurred between two families. "Despite the homogeneity of the French-Canadian population as compared to other populations and similarities seen within families, we realize that copy number variants are very different between families with no genealogical connection. From a genetic point of view, the diseases we looked at are a "family affair."

Moreover, although the study focused on the aortic valve area, genes explaining associated conditions have been identified. "It is striking that the majority of the identified genes also play an important role in blood vessels, not just in the valves of the heart," says Dr. Andelfinger. Indeed, the images are of striking clarity: expression patterns of the genes identified selectively stain areas of the heart where lesions are observed. "Numerous patients continue to have problems after successful initial intervention on the aortic valve, such as aortic dilation. Our study sheds new light on the link between the two issues, something we always observed clinically but had a hard time to explain," he concludes.

Explore further: Study identifies second gene associated with specific congenital heart defects

Related Stories

Study identifies second gene associated with specific congenital heart defects

April 29, 2011
A gene known to be important in cardiac development has been newly associated with congenital heart malformations that result in obstruction of the left ventricular outflow tract. These are the findings from a study conducted ...

Researchers link chromosome region to thoracic aortic disease

June 16, 2011
Patients with thoracic aortic aneurysms that lead to acute aortic dissections are 12 times more likely to have duplications in the DNA in a region of chromosome 16 (16p13.1) than those without the disease, according to a ...

New mouse model helps explain gene discovery in congenital heart disease

June 26, 2012
Scientists now have clues to how a gene mutation discovered in families affected with congenital heart disease leads to underdevelopment of the walls that separate the heart into four chambers. A Nationwide Children's Hospital ...

Recommended for you

Discovery of the 'pioneer' that opens the genome

January 23, 2018
Our genome contains all the information necessary to form a complete human being. This information, encoded in the genome's DNA, stretches over one to two metres long but still manages to squeeze into a cell about 100 times ...

Genes contribute to biological motion perception and its covariation with autistic traits

January 22, 2018
Humans can readily perceive and recognize the movements of a living creature, based solely on a few point-lights tracking the motion of the major joints. Such exquisite sensitivity to biological motion (BM) signals is essential ...

Researchers identify gene responsible for mesenchymal stem cells' stem-ness'

January 22, 2018
Many doctors, researchers and patients are eager to take advantage of the promise of stem cell therapies to heal damaged tissues and replace dysfunctional cells. Hundreds of ongoing clinical trials are currently delivering ...

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

Two new breast cancer genes emerge from Lynch syndrome gene study

January 18, 2018
Researchers at Columbia University Irving Medical Center and NewYork-Presbyterian have identified two new breast cancer genes. Having one of the genes—MSH6 and PMS2—approximately doubles a woman's risk of developing breast ...

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.