Atypical COL3A1 variants (glutamic acid to lysine) cause vascular Ehlers–Danlos syndrome with a consistent phenotype of tissue fragility and skin hyperextensibility

The Ehlers-Danlos syndromes (EDS) are a group of rare inherited connective tissue disorders. Vascular EDS (vEDS) is caused by pathogenic variants in COL3A1, most frequently glycine substitutions. We describe the phenotype of the largest series of vEDS patients with glutamic acid to lysine substitutions (Glu>Lys) in COL3A1, which were all previously considered to be variants of unknown significance.Clinical and molecular data for seven families...