Novel Variants in Five Families with Aortic/Arterial Aneurysm and Dissection with Variable Connective Tissue Findings.

Thoracic aortic aneurysm and dissection (TAAD) is a major cause of cardiovascular morbidity and mortality. Loss-of-function variants in , encoding the extracellular matrix crosslinking enzyme lysyl oxidase, have been reported to cause familial TAAD. Using a next-generation TAAD gene panel, we identified five additional probands carrying variants, including two missense variants affecting highly conserved amino acids in the catalytic domain and three truncating variants. Connective tissue manifestations are apparent in a substantial fraction of the variant carriers. Some variant carriers presented with TAAD early in life, while others had normal aortic diameters at an advanced age. Finally, we identified the first patient with spontaneous coronary artery dissection carrying a variant. In conclusion, our data demonstrate that loss-of-function variants cause a spectrum of aortic and arterial aneurysmal disease, often combined with connective tissue findings.