{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:40:29Z","timestamp":1779291629764,"version":"3.51.4"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:00:00Z","timestamp":1689552000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Vascular Ehlers\u2010Danlos syndrome (vEDS) is an autosomal dominant disease caused by aberrations in <jats:italic>COL3A1<\/jats:italic>, which encodes type III collagen. Sanger sequencing has limitations for diagnosis since exon deletion\/duplication and splicing alterations are not uncommon in <jats:italic>COL3A1<\/jats:italic>. We report 2 patients with vEDS who were not diagnosed by conventional Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed either targeted panel or whole\u2010genome 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2010109_1923+10del). On targeted panel sequencing in the other patient, we found a novel intronic variant of c.1149+6T&gt;C that leads to skipping of exon 16 (r.1051_1149del) by cDNA sequencing. SpliceAI showed 98.8% sensitivity for known splicing variants in <jats:italic>COL3A1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2240","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T05:16:20Z","timestamp":1689657380000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of two novel <i>COL3A1<\/i> variants in patients with vascular Ehlers\u2010Danlos syndrome"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2695-9634","authenticated-orcid":false,"given":"Won Young","family":"Heo","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Genetics, Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul South 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