GENETIC EVALUATION
Genetic testing is the definitive tool for confirming the diagnosis of vEDS, Sanger sequencing of COL3A1 was undertaken, and pathological variants were identified. (Fig.2) The gene is 38 kb long and has 51 exons, which are numbered 1–51 to match the numbering of exons in the genes for other fibrillar collagens (Fig.3). In contrast, sequencing of COL3A1 identified new variant; c.4223C>T p.F1408S in exons 50 respectively (Fig.4) . After searching some database, like Google scholar, PubMed, Ehlers-Danlos Syndrome variant Database, Human Gene Mutation Database, gnom AD and ClinVar, we confirmed that this variant has not been previously reported. COL3A1 mutations introduce premature termination codons that lead to mRNA instability[7].The mutation of COL3A1 resulting in the defective synthesis of the type III collagen Pro A1 (III) chain. Most of the COL3A1 mutations were led to substitutions for glycine in the repeated Gly-X-Y triple motif of the triple-helical domain[7]. (Fig.4)
DISCUSSION
In this study, we applied whole-exome sequencing (WES) and Sanger sequencing and identified a new mutation in COL3A1(c.4223C>T p.F1408S) that led to vEDS.
vEDS is a rare, severe, autosomal dominant disease characterised by arterial dissections, arterial ruptures, bowel perforation, and organ ruptures [8,9]. The incidence of vEDS is 1/50,000-1/200000[4], the median survival has been reported at 24.6 and 48 years[9], and the cause of death is associated with arterial aneurysm and,or spontaneous rupture of dissection.The major cause of vEDS is mutations in COL3A1.
After sequencing of COL3A1 mutation was found in our patient, the diagnosis of vEDS was effectively confirmed with the identification of rare biallelic variants in COL3A1. Novel compound heterozygous COL3A1 variants c.4223C>T p.F1408S in exons 50 was found.
The detailed pathogenesis underlying the COL3A1 mutation causing vEDS has not been elucidated so far. Our report novel compound heterozygous COL3A1 variants associated with Vascular Ehlers-Danlos Syndrome, thereby expanding the associated molecular spectrum and emphasising the devastating nature of this multi-system disease, and hoping to shed light on the mechanism how COL3A1 mutation causes vEDS.
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