Researchers at UTHealth Houston have identified genetic variants linked to a rare form of bicuspid aortic valve disease affecting young adults. The study, published in the American Journal of Human Genetics, reveals that these variants can lead to severe and potentially life-threatening aortic complications.
"We previously found that young individuals who present due to early onset thoracic aortic dissections are more likely to have bicuspid aortic valves and more likely to have rare variants in bicuspid aortic valve-associated genes," said Siddharth Prakash, MD, PhD, co-principal investigator of the study and associate professor of medical genetics and cardiovascular medicine at McGovern Medical School at UTHealth Houston. "When we observed that bicuspid aortic valve is kind of a risk marker for this group with bad outcomes, we specifically wanted to see whether young individuals who present clinically due to problems related to bicuspid aortic valve disease may also have rare genetic variants that predict complications such as needing valve surgery."
Approximately 1 in 100 people are born with a bicuspid aortic valve, making it the most common cause of congenital heart disease. This condition results in the valve having two flaps instead of three, leading to improper opening and closing with each heartbeat. Potential complications include blocked or reduced blood flow through the heart chambers, shortness of breath, chest pain, fainting, difficulty exercising, and in severe cases, an aortic dissection.
The study focused on individuals under 30 presenting specific complications or those with immediate relatives affected by early onset bicuspid aortic valve disease. Early onset symptoms included moderate or severe aortic stenosis or regurgitation, large thoracic aortic aneurysms requiring surgery, or an aortic dissection.
Prakash's team analyzed whole-exome sequencing data from 215 families across over 20 institutions to identify rare genetic variants associated with congenital heart disease in early onset cases. They compared these findings with those from patients with later-onset disease.
"We showed that older patients with bicuspid aortic valves are unlikely to benefit from genetic testing because they are unlikely to have these kinds of genetic variants," Prakash noted. "It's important for people to realize...that many people with bicuspid aortic valves have affected relatives."
The research was funded by the National Institutes of Health (R01HL137028, R21HL150383, R01HL114823, and R21HL150373) and supported by sequencing and data analysis from the University of Washington Center for Rare Disease Research.
Co-principal investigator Dianna M. Milewicz, MD, PhD; first author Sara Mansoorshahi; and additional authors contributed significantly to this study from various prestigious institutions globally.
