A Possible Phenotype-to-Genotype Association of Novel Single-Nucleotide Variants in the Coding Exons of the Gene to Arterial Aneurysmal and Dissection Diseases.

After reporting the first known clinical case associating compound heterozygous single-nucleotide variants in Exon 2 of to aortic aneurysmal and iliac dissection, we began prospective surveillance in our vascular genetic practice for similar cases. Herein, we present nine (9) subjects from a total cohort of 135 with arterial aneurysms or dissections who revealed single-nucleotide variants in with no other alterations in a panel of 35 genes associated with aneurysmal and dissection disorders. Five out of nine (5/9) single-nucleotide variants were in Exon 1, and four out of nine (4/9) mutations were in Exon 2, both of which are principal coding exons for this gene. Eight out of nine (8/9) were ACMG variants of unknown significance (VUSs), and one out of nine (1/9) was an ACMG pathogenic mutation previously associated to brittle cornea syndrome (BCS). Of our nine subjects, four (44.4%) experienced clinically significant vascular dissection, and four (44.4%) had a family history of one or more first-degree relatives with aneurysmal or dissection diseases. This novel genetic case series significantly strengthens our initial discovery of potential association with arterial aneurysmal/dissection diseases through the study of this cohort of unrelated patients.