Case report: Characterization of a rare pathogenic variant associated with loss of COL3A1 expression in vascular Ehlers Danlos syndrome.

The vascular subtype of Ehlers Danlos Syndrome (vEDS) is a rare connective tissue disorder characterized by spontaneous arterial, bowel or organ rupture. The diagnosis of vEDS is established in a proband by identification of a heterozygous pathogenic variant in the alpha-1 gene of type III collagen () by molecular analysis. In this report, we present a case of vEDS with life threatening, spontaneous arterial dissections in association with an uncharacterized rare variant of > . Primary culture of patient skin fibroblasts followed by immunofluorescence revealed a complete absence of COL3A1 protein expression as well as altered morphology. Electron microscopy of the cultured fibroblasts showed abnormal vacuoles in the cytoplasm suggestive of a secretory defect. In this study, we have performed functional characterization of the > variant for the first time and this may now be classified as likely pathogenic in vEDS. *Both JM and LRL contributed equally in the manuscript and should both be considered as the first author.