Recurrent Coronary Artery Fistulae and a Novel Transforming Growth Factor Beta-3 Mutation

Loeys-Dietz syndrome (LDS) is a rare connective tissue disease associated with mutations in transforming growth factor (TGF) signaling leading to an increased risk of arterial calcification, aneurysms, and/or dissections. We report a case in which genetics evaluation revealed a rare variant E244K in the TGFB3 gene. The variant leads to the substitution of glutamic acid for lysine, two amino acids with dissimilar properties. Analysis from evolutionary data shows the glutamic acid is maintained across species. The clinical significance of the E244K variant in association with LDS was never previously reported as pathologic. This case report aims to report that the significance of the E244K variant in the TGFB3 gene is found to he pathologic in our case. A search on the Genome Aggregation Database (gnomAD) did not reveal any previously identified individuals with this variant, despite being a well-covered region. ClinVar has a few entries for E244K, where most of them are listed as unknown significance. Bringing together the genotype evidence with our patient's clinical picture, we consider the variant to be pathogenic for this family.

Automated summary

Loeys-Dietz syndrome is a rare connective tissue disease associated with mutations in transforming growth factor signaling, leading to an increased risk of arterial calcification, aneurysms, and/or dissections. A rare variant E244K in the TGFB3 gene was identified in a case report, with evidence suggesting it is pathogenic.