{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T15:14:12Z","timestamp":1787843652117,"version":"build-2784847793"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder primarily affecting the cardiovascular, ocular, and skeletal systems. Cardiovascular complications are the leading cause of mortality in MFS. Mutations in the <jats:italic>FBN1<\/jats:italic> gene, which encodes fibrillin-1, a critical extracellular matrix protein, are the predominant cause of the disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>On March 11, 2024, we diagnosed a 30-year-old female proband with MFS based on the revised Ghent criteria, presenting with aortic root aneurysm, aortic dissection, multiple skeletal abnormalities, and a family history of MFS. Whole-exome sequencing followed by Sanger sequencing confirmation identified a novel inherited insertion mutation (c.4991dupA) in exon 40 of the <jats:italic>FBN1<\/jats:italic> gene. We performed valve-sparing aortic root replacement (David Procedure) and total aortic arch replacement using a tetrafurcated graft, along with the implantation of a specially designed frozen elephant trunk in the descending aorta (Sun's Procedure). Postoperatively, the patient underwent biweekly clinical follow-ups for three months. No treatment-related adverse events were reported during the monitoring period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The diagnosis of MFS requires an integrated approach, combining clinical manifestations, imaging studies, and genetic analysis. This novel mutation is associated with severe skeletal manifestations and life-threatening cardiovascular abnormalities, underscoring its clinical relevance. Its association with aggressive phenotypes enhances genotype-phenotype correlations. Importantly, these findings highlight the imperative need for early intervention in high-risk individuals by bridging genetic discovery to clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2025.1533138","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T04:10:30Z","timestamp":1745381430000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case Report: A FBN1 frameshift-and-nonsense mutation and aortic dissection in Marfan syndrome"],"prefix":"10.3389","volume":"12","author":[{"given":"Chao","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjun","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haocheng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zanxin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minxin","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00298-7","article-title":"Marfan syndrome","volume":"7","author":"Milewicz","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B2","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13023-017-0754-6","article-title":"The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome","volume":"13","author":"Becerra-Mu\u00f1oz","year":"2018","journal-title":"Orphanet J Rare Dis"},{"key":"B3","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.gene.2016.07.033","article-title":"Fbn1: the disease-causing gene for Marfan syndrome and other genetic disorders","volume":"591","author":"Sakai","year":"2016","journal-title":"Gene"},{"key":"B4","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1186\/s13023-024-03139-4","article-title":"Causative role of a novel intronic indel variant in Fbn1 and maternal germinal mosaicism in Marfan syndrome","volume":"19","author":"Bai","year":"2024","journal-title":"Orphanet J Rare Dis"},{"key":"B5","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/352337a0","article-title":"Marfan Syndrome caused by a recurrent de novo missense mutation in the fibrillin gene","volume":"352","author":"Dietz","year":"1991","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/s0065-3233(05)70012-7","article-title":"Fibrillin microfibrils","volume":"70","author":"Kielty","year":"2005","journal-title":"Adv Protein Chem"},{"key":"B7","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1186\/s12887-023-04357-8","article-title":"Genotype-phenotype spectrum and prognosis of early-onset Marfan syndrome","volume":"23","author":"Kemezyte","year":"2023","journal-title":"BMC Pediatr"},{"key":"B8","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s12920-022-01213-z","article-title":"Association of gene polymorphisms in Fbn1 and tgf-\u0392 signaling with the susceptibility and prognostic outcomes of Stanford type B aortic dissection","volume":"15","author":"Sun","year":"2022","journal-title":"BMC Med Genomics"},{"key":"B9","volume-title":"Marfan Syndrome. 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