We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The ACTA2 gene makes a protein called smooth muscle alpha (ɑ)-2 actin (ɑ-2 actin). The ɑ-2 actin protein is found primarily in our smooth muscles (muscles that line our blood vessels, stomach, intestines, and other internal organs). Smooth muscles relax and contract automatically as part of their normal function, and the ɑ-2 actin protein works with other proteins to help the smooth muscles contract, which helps them to keep their shape instead of stretching out too much while blood is pumping through.
If someone has a harmful change (called a pathogenic variant) in one of their ACTA2 genes, then their body does not make as much ɑ-2 actin protein as it should. If there is not enough ɑ-2 actin protein, then the smooth muscles cannot contract as well as they should. This causes damage to these muscles, which can lead to health issues likefamilial thoracic aortic aneurysm and dissection. Some specific pathogenic variants in the ACTA2 gene can also cause other health issues like patent ductus arteriosus and coarctation of the aorta.
Pathogenic variants in the ACTA2 gene are passed through a family in anautosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the ACTA2 gene and have the same chances to inherit and pass down pathogenic variants.
Genetic testing for pathogenic variants in ACTA2 is currently available, but there are a few different ways to approach testing: