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Severe cardiovascular manifestations (i.e., aortic aneurysm and dissection) are the most life\u2010threatening complications. Most of the cases are caused by mutations, a minor group of which are copy number variations (CNV), in the <jats:italic>FBN1<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Multiplex ligation\u2010dependent probe amplification test was performed to detect CNVs in 41 MFS patients not carrying disease\u2010causing mutations in <jats:italic>FBN1<\/jats:italic> gene. Moreover, the association was analyzed between the localization of CNVs, the affected regulatory elements and the cardiovascular phenotypes among all cases known from the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A large two\u2010exon deletion (exon 46 and 47) was identified in two related patients, which was associated with a mild form of cardiovascular phenotype. Severe cardiovascular symptoms were found significantly more frequent in patients with <jats:italic>FBN1<\/jats:italic> large deletion compared to our patients with intragenic small scale <jats:italic>FBN1<\/jats:italic> mutation. Bioinformatic data analyses of regulatory elements located within the <jats:italic>FBN1<\/jats:italic> gene revealed an association between the deletion of STAT3 transcription factor\u2010binding site and cardiovascular symptoms in five out of 25 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrated that large CNVs are often associated with severe cardiovascular manifestations in MFS and the localization of these CNVs affect the phenotype severity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2166","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T04:44:21Z","timestamp":1679460261000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Correlation between large <i>FBN1<\/i> deletions and severe cardiovascular phenotype in Marfan syndrome: Analysis of two novel cases and analytical review of the 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