Rare genetic variants associated with bicuspid aortic valve disease in young adults identified

Genetic variants associated with a rare form of bicuspid aortic valve disease that affects young adults and can lead to dangerous and potentially life-threatening aortic complications have been identified by UTHealth Houston researchers.

This study was published in the journal American Journal of Human Genetics.

“We previously found that young people presenting for early-onset thoracic aortic dissection were more likely to have bicuspid aortic valves and more likely to have rare variants of aortic valve-related genes,” said Siddharth Prakash, PhD, PhD. have another , the study’s principal investigator and associate professor of medical genetics and cardiovascular medicine in the department of internal medicine at the McGovern School of Medicine at UTHealth Houston.

Once we observed that bicuspid aortic valve was somewhat of a risk marker for this group with poor outcomes, we specifically wanted to see whether young people presenting clinically with problems related to bicuspid aortic valve disease might have rare genetic variants that predict complications. Like needing valve surgery.”

1 in 100 people are born with a bicuspid aortic valve, making it the most common cause of congenital heart disease.

Comparing the rare subtype of early-onset bicuspid aortic valve with the general population of the disease allowed researchers to determine which groups of patients would benefit from genetic testing, enabling earlier and more aggressive treatment.

Patients with bicuspid aortic valve disease often wait too long to be seen, leading to more severe cardiovascular symptoms such as heart failure and even sudden death, researchers say.

A bicuspid aortic valve is a congenital heart defect in which it has two flaps or cusps instead of three, so the valve does not open and close properly with each heartbeat. This can lead to complications such as blockage, reduced or delayed blood flow in the chambers of the heart, causing shortness of breath, chest pain, fainting and difficulty exercising. In more severe cases, the disease can lead to aortic dissection or aortic rupture, which is a life-threatening condition.

The researchers studied people who had specific complications of the disease before the age of 30 or were close relatives of someone with early-onset bicuspid aortic valve disease. Initial disease symptoms were defined as moderate or severe aortic stenosis or aortic insufficiency, large thoracic aortic aneurysm, need for aortic surgery or aortic dissection.

The researchers aim to identify genetic variants that may lead to an increased risk of developing the disease in young adults. “The average person in this study was diagnosed in their 20s and had relatives with the disease, so we traced the onset of the disease in families and reported rare genetic variants associated with the disease in these participants,” Prakash said. And their relatives are separated.” said

Prakash and his team analyzed whole-exome sequencing data obtained from 215 families from more than 20 institutions to identify rare genetic variants that cause congenital heart disease in this rare subgroup of early-onset bicuspid aortic valve disease. can be identified. They compared these findings with the more common population of patients with bicuspid aortic valve disease.

The genes identified included genes that cause non-syndromic isolated bicuspid aortic valve as well as other types of congenital heart disease associated with bicuspid aortic valve or related congenital anomalies. The researchers found deleterious gene variants with moderate or strong evidence for developmental cardiac phenotypes in 107, or 50 percent, of the affected families in the study.

“We showed that older patients with bicuspid aortic valves are unlikely to benefit from genetic testing because they are unlikely to have these genetic variants,” Prakash said.

It’s important for people to know that, as we saw in this study, many people with bicuspid aortic valve have affected relatives. In the future, family members may be tested for genetic variants that cause bicuspid aortic valve complications. Can these genetic variants be treated earlier to prevent further complications.”