Next-generation sequencing and a novel COL3A1 mutation associated with vascular Ehlers-Danlos syndrome with severe
Francesca Cortini1,2, Barbara Marinelli3, Manuela Seia4
1Department of Clinical Sciences and Community Health, University of Milan IRCCS Ca' Granda Foundation, Via San Barnaba 8, 20122, Milano, Italy. francesca.cortini@guest.unimi.it.
Insights
A new COL3A1 gene mutation, c.1493G>A (p.G498D), is linked to vascular Ehlers-Danlos syndrome. This discovery aids understanding of genotype-phenotype correlations in this severe connective tissue disorder.
Area of Science:
- Genetics
- Molecular Biology
- Medical Science
Background:
- Vascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant disorder.
- It stems from COL3A1 gene mutations affecting type III collagen.
- vEDS leads to severe connective tissue fragility, risking arterial and intestinal ruptures.
Observation:
- A case study of a 38-year-old Italian woman with vEDS.
- Genetic analysis identified a novel COL3A1 mutation: c.1493G>A, p.G498D in exon 21.
- This heterozygous mutation alters glycine-X-Y repeats in type III procollagen.
Findings:
- A new mutation in the COL3A1 gene associated with vEDS has been identified.
- The mutation p.G498D disrupts critical glycine residues in type III procollagen.
- This finding contributes to understanding vEDS pathogenesis.
Implications:
- This research enhances understanding of genotype-phenotype correlations in vEDS.
- Identifying novel mutations aids in accurate diagnosis and risk assessment.
- Further research can explore therapeutic strategies targeting COL3A1 mutations.
Background:
The vascular type of Ehlers-Danlos syndrome is an autosomal dominant connective tissue disorder caused by a mutation in the COL3A1 gene encoding pro-alpha1 chain of type III collagen. The vascular type of Ehlers-Danlos syndrome causes severe fragility of connective tissues with arterial and intestinal ruptures and complications in surgical and radiological treatments.
Case Presentation:
We present a case of a 38-year-old Italian woman who was diagnosed as having the vascular type of Ehlers-Danlos syndrome. Genetic testing, conducted by Target Enrichment approach (Agilent Technologies), identified a new mutation c.1493G>A, p.G498D in exon 21 of COL3A1 gene (heterozygous state). This mutation disrupts the normal glycine-X-Y repetitions of type III procollagen by converting glycine to aspartic acid.
Conclusions:
We report a new genetic mutation associated with the vascular type of Ehlers-Danlos syndrome. We also describe clinical and genetic findings that are important to understand the genotype/phenotype correlation in patients with the vascular type of Ehlers-Danlos syndrome.
