Human aortic aneurysm genomic dictionary: is it possible?

Abstract

Thoracic aortic aneurysm (TAA), a typically silent but frequently lethal disease, is strongly influenced by underlying genetics. Approximately 30 genes have been associated with syndromic and non-syndromic familial thoracic aortic aneurysm and dissection (TAAD) to date. An estimated 30% of patients with non-syndromic familial TAAD, which is typically inherited in an autosomal dominant manner, have a mutation in one of these genes. The underlying genetic mutation helps predict patients' clinical presentation, risk of aortic dissection at small aortic sizes (< 5.0cm), and risk of other cardiovascular disease. As a result, a TAAD genomic dictionary based on these genes is necessary to provide optimal patient care, but is not on its own sufficient as this disease is typically inherited with reduced penetrance and has widely variable expressivity. Next-generation sequencing has been and will continue to be critical for identifying novel genes and variants associated with TAAD as well as genotype-phenotype correlations that will allow for management to be targeted to not only the underlying gene harboring the pathogenic variant but also the specific mutation identified. The aortic dictionary, to which a clinician can turn to obtain information on clinical consequences of a specific genetic variants, is not only possible, but has been substantially written already. As additional entries to the dictionary are made, truly personalized, genetically based, aneurysm care can be delivered.