An international team of researchers has discovered that mutations in the MINDBOMB1 homologue gene MIB1 may be causative for bicuspid aortic valve, a relatively common congenital heart condition.
Around one to two percent of the population are born with a bicuspid rather than a tricuspid aortic valve. This means these individuals only have two valve leaflets rather than three, which puts them at higher risk for cardiovascular conditions such as blockage or narrowing of the aorta and endocarditis, or inflammation of the heart due to infection.
Although bicuspid aortic valve can be inherited, there is little known about the genes involved. In this study, published in the journal JAMA Cardiology, the research team looked for candidate genes and variants by testing 938 people with the condition using exome sequencing and gene prioritization tools.
The researchers discovered rare variants in the MIB1 gene in 2% of cases versus 0.9% of controls and predicted these variants to be damaging.
They also carried out replication studies to test their findings and expressed some of the variants they discovered in mice models, which also developed with the bicuspid aortic valve phenotype.
MIB1 is important in the NOTCH pathway “an evolutionarily conserved cell-cell communication signaling pathway involved in multiple developmental processes,” write the authors.
“NOTCH signaling regulates aortic valve morphogenesis, and its disruption causes aortic valve diseases in both humans and mice.” MIB1 protein induces NOTCH ligand ubiquitination and endocytosis.
Knowing more about the genetics of bicuspid aortic valve is helpful for researchers and clinicians, as they can look for mutations in this gene in future. It may also be possible to develop therapies targeting this gene.
“This is an especially exciting prospect because bicuspid aortic valve is the most frequent congenital defect. In addition to helping patients, alternatives to surgery could reduce the cost burden on health care systems,” said co-corresponding author José Luis de la Pompa, a group leader at the Centro Nacional de Investigaciones Cardiovasculares Carlos III in Madrid, in a press statement.
