Novel compound heterozygous COL3A1 variants are associated with Vascular
Ehlers-Danlos Syndrome
Abstract
Aim: Vascular Ehlers-Danlos Syndrome (vEDS) is an autosomal-
dominant inherited disorder result on collagen type III alpha-1 chain
(COL3A1) gene mutation. vEDS is associated with a decreased life
expectancy due to spontaneous arterial, intestinal, and uterine rupture.
The diagnosis of vEDS is supported by genetic testing confirming the
presence of pathogenic variations in COL3A1. Although how COL3A1
mutation in the precise mechanism can lead to the multiple vascular
involvements seen at a pathological level remains unclear. COL3A1
encodes the Collagen alpha-1(III) chain in humans. The alterations in
content and properties of type III collagen, can lead to organ
fragility. Genome sequencing revealed heterozygous COL3A1 variants
(c.4223C>T p.F1408S ) as likely genetic cause of vEDS in
this present case. Methods: We assessed the young adult
diagnosed with Stanford A aortic dissection without a history of
hypertension and undertook Sanger sequencing. Results: We
identified novel compound heterozygous variant in COL3A1: a missense-
c.4223C>T p.F1408S Conclusion: Given the clinical phenotype
and identified variants we suggest that this is the first patient
reported to date with vEDS due to c.4223C>T mutations in
COL3A1.