{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T16:57:02Z","timestamp":1767373022513,"version":"3.41.2"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T00:00:00Z","timestamp":1744416000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Vascular Ehlers\u2013Danlos syndrome (vEDS) is caused by alterations in the <jats:italic>COL3A1<\/jats:italic> gene, typically involving missense variants that replace glycine residues. In contrast, short <jats:italic>in\u2010frame<\/jats:italic> insertions, deletions, and duplications are rare and pose significant challenges for investigation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The histological examination of vascular tissue from a 26\u2010year\u2010old man, who died from a common iliac artery aneurysm and whose mother died at age 60 from an abdominal aortic dissection, strongly suggested a diagnosis of Ehler\u2013Danlos type IV. Ex\u00a0vivo collagen phenotype assessment, molecular analysis, and in silico structural studies of type III collagen were subsequently performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ex vivo analysis of the patient's fibroblasts revealed altered collagen synthesis, whereas the molecular testing identified a novel 18\u2010nucleotide <jats:italic>in\u2010frame<\/jats:italic> duplication (c.2868_2885dup\u2010GGGTCTTGCAGGACCACC) in the <jats:italic>COL3A1<\/jats:italic> gene, resulting in a six\u2010amino acid insertion, p.(Leu958_Gly963dup). Structural investigation indicated that this duplication led to a local perturbation of the collagen triple helix near a metalloproteinase cleavage site.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study highlights the pathogenic role of a novel <jats:italic>in\u2010frame<\/jats:italic> duplication in the <jats:italic>COL3A1<\/jats:italic> gene, demonstrating how this seemingly benign alteration significantly compromises collagen turnover and contributes to the development of vEDS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70095","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T07:25:22Z","timestamp":1744442722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification and Structural Characterization of a Novel <i>COL3A1<\/i> Gene Duplication in a Family With Vascular Ehlers\u2013Danlos Syndrome"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5084-295X","authenticated-orcid":false,"given":"Gianmaria","family":"Miolo","sequence":"first","affiliation":[{"name":"Medical Oncology and Cancer Prevention Unit Centro di Riferimento Oncologico di Aviano (CRO), IRCCS  Aviano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piernicola","family":"Machin","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Medicine Laboratory Section Pordenone Hospital  Pordenone Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9012-7158","authenticated-orcid":false,"given":"Marco","family":"De Conto","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, Centre of Excellence in Biocrystallography University of Trieste  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Fortuna","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, Centre of Excellence in Biocrystallography University of Trieste  Trieste Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Viglio","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Biochemistry Unit University of Pavia  Pavia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara","family":"Della Puppa","sequence":"additional","affiliation":[{"name":"Oncogenetics and Functional Oncogenomics Unit Centro di Riferimento Oncologico di Aviano (CRO), IRCCS  Aviano Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-5113","authenticated-orcid":false,"given":"Silvano","family":"Geremia","sequence":"additional","affiliation":[{"name":"Department of Chemical 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