Nav: Home

Turning to genetics to treat little hearts

December 16, 2019

A team of researchers at CHU Sainte-Justine and Université de Montréal has discovered a new mechanism involved in a common congenital disease of the aortic valve. The findings of the study, conducted in collaboration with the Hadassa Hebrew University Medical Center, were published in the prestigious journal Nature Genetics.

Valve disease affects two percent of the population, which is a significant proportion. Despite this high incidence and many signs that point to the role played by genetics in aortic diseases, only a few genes have been identified to date. In this case, a gene known as ADAMTS19 was shown to be involved in an aortic valve disease.

"Valve diseases can affect one of the heart's four valves - the tricuspid, pulmonary, mitral or aortic valve. We looked at patients with a bicuspid aortic valve, which is an aortic valve that has only two functional leaflets instead of the usual three," explained Dr. Gregor Andelfinger, a pediatric cardiologist and researcher at CHU Sainte-Justine and at Universite de Montreal. Most patients affected by this valve disease are asymptomatic in early life. But in adulthood, this bicuspid valve can leak or cause premature aortic narrowing, resulting in shortness of breath or abnormal fatigue on exertion.

This discovery was made in the course of following a family at CHU Sainte-Justine; two of the three siblings in this family have this congenital variation, which helped to identify the culprit ADAMTS19 gene. Up to now, this gene had virtually never been characterized by a medical team, not to mention associated with this disease.

"To understand the role of this gene, we had to use a preclinical model that presented the same pathological features as our young patients. This helped us to analyze the function of this gene in great detail and to define the mechanisms of the disease," explained Florian Wünnemann, PhD and the lead author of the study.

"By using single cell sequencing, a new technology that establishes the genetic profile of a single cell - in heart tissue, for example - we can very precisely define the type of cell behind the pathology. This really helped us demonstrate the molecular consequences of the mutation," he added.

Indeed, the data shows that the mutation in patients changes the regulatory mechanism in the valves. One thing leading to another, an Israeli team of researchers at the Hadassa Hebrew University Medical Center that had identified exactly the same gene contacted Dr. Andelfinger and his team, lending support to their hypothesis.

An estimated 4,000 valve surgeries are performed in Canada each year, and this figure is constantly rising due to ageing of the population. On top of the pain and suffering of patients and their families, the economic burden is close to $1 billion a year.

CHU Sainte-Justine is a leading provincial centre of expertise in rare genetic diseases in terms of the quality and number of its research projects, its clinical management and knowledge transfer. The discovery of the genetic causes of some 40 rare diseases by the teams at CHU Sainte-Justine in recent years is a shining example of this expertise.
-end-
About the study

The article "Loss of ADAMTS19 causes progressive non-syndromic heart valve disease" was published in the journal Nature Genetics on December 16th, 2019. The lead author is Florian Wünnemann, a former PhD student under the supervision of Dr. Gregor Andelfinger. The principal investigator is Dr. Gregor Andelfinger, Associate Professor in the Department of Pediatrics at Université de Montréal, and Cardiologist Pediatrician, Researcher, and Head of Research Axis, Fetomaternal and Neonatal Pathologies at the CHU Sainte-Justine Research Center.

The study received support from the Heart and Stroke Foundation of Canada, the Leducq Foundation, the National Bank Research Chair in Cardiovascular Genetics and the Fonds de recherche du Québec - Santé.

About the CHU Sainte-Justine Research Centre

CHU Sainte-Justine Research Centre is a leading mother-child research institution affiliated with Université de Montréal. It brings together more than 200 research investigators, including over 90 clinicians, as well as 350 graduate and post-graduate students focused on finding innovative means of prevention, faster and less invasive treatments, and personalized approaches to medicine. The Centre is part of CHU Sainte-Justine, which is the largest mother-child hospital in Canada and second most important pediatric hospital in North America.

University of Montreal

Related Science Articles:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.
Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.
Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.
Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.
World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.
PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.