Genetic factors play some part in nearly all health conditions and characteristics. However, there are some conditions in which these factors are almost fully responsible for causing the condition. These are called genetic disorders, or inherited disorders. Some groups of inherited disorders can present similar symptomatic findings in individuals. To ensure proper care in these individuals, it is important to determine the genetic origin of their disorders to facilitate proper treatment. Classical Sanger sequencing using a gene-by-gene approach can be time-consuming and expensive. An enrichment method utilizing next-generation sequencing (NGS), on the other hand, can be faster and more economical.
An example of a group of complex disorders affecting the aorta is aortopathy. The aorta is the largest artery in the human body. It carries oxygenated blood from the heart to other parts of the body. Disruption to one or more elements of the cytoskeleton-receptor-extra cellular matrix (ECM) complex can affect aortic wall homeostasis, changing both the structure and mechanical properties of the aorta.
Although the FBN1 gene, whose mutations cause Marfan syndrome, plays a major role in aortopathy pathogenesis, several other genes are known to be involved. For example, COL3A1 mutations cause a related syndrome called Ehlers-Danlos syndrome type IV, and mutations in ACTA2 and MYH11 cause thoracic aortic aneurysms or TAAs (Figure 1).