AUTHOR=Manhas Janvie , Lohani Lov Raj , Seethy Ashikh , Kumar Uma , Gamanagatti Shivanand , Sen Sudip TITLE=Case report: Characterization of a rare pathogenic variant associated with loss of COL3A1 expression in vascular Ehlers Danlos syndrome JOURNAL=Frontiers in Cardiovascular Medicine VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.939013 DOI=10.3389/fcvm.2022.939013 ISSN=2297-055X ABSTRACT=

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 (COL3A1) 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 COL3A1, exon19:c.1340G > A. 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 COL3A1 exon19:c.1340G > A variant for the first time and this may now be classified as likely pathogenic in vEDS.