We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Identification of two novel COL3A1 variants in patients with vascular Ehlers‐Danlos syndrome.
- Authors
Heo, Won Young; Jang, Shin Yi; Park, Taek Kyu; Ki, Chang‐Seok; Kim, Jong‐Won; Kim, Duk‐Kyung; Jang, Ja‐Hyun
- Abstract
Background: Vascular Ehlers‐Danlos syndrome (vEDS) is an autosomal dominant disease caused by aberrations in COL3A1, which encodes type III collagen. Sanger sequencing has limitations for diagnosis since exon deletion/duplication and splicing alterations are not uncommon in COL3A1. We report 2 patients with vEDS who were not diagnosed by conventional Sanger sequencing. Methods: We performed either targeted panel or whole‐genome sequencing. Complementary DNA (cDNA) sequencing was performed using cultured skin fibroblasts. Sanger sequencing of DNA was performed for the confirmation of breakpoints in the case of exon deletion. We also evaluated the sensitivity of the splicing prediction tool, SpliceAI. Results: An exon 27 deletion was suspected on targeted panel sequencing of 1 patient. The deletion was confirmed using cDNA sequencing (r.1870_1923del) and breakpoints were confirmed (c.1870‐109_1923+10del). On targeted panel sequencing in the other patient, we found a novel intronic variant of c.1149+6T>C that leads to skipping of exon 16 (r.1051_1149del) by cDNA sequencing. SpliceAI showed 98.8% sensitivity for known splicing variants in COL3A1. Conclusion: Our study highlights the necessity of a comprehensive approach to the genetic diagnosis of vEDS. In addition, cDNA sequencing was useful as an auxiliary method, especially considering the limited sensitivity of the splicing prediction tool.
- Subjects
EHLERS-Danlos syndrome; NUCLEOTIDE sequencing; COMPLEMENTARY DNA; DNA sequencing; GENETIC disorder diagnosis
- Publication
Molecular Genetics & Genomic Medicine, 2023, Vol 11, Issue 9, p1
- ISSN
2324-9269
- Publication type
Case Study
- DOI
10.1002/mgg3.2240