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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