{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:55:23Z","timestamp":1785819323045,"version":"3.56.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"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. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Marfan Syndrome (MS) is a connective tissue disorder, an autosomal dominant condition mostly caused by variants in the <jats:italic>FBN1<\/jats:italic> gene, which encodes for fibrillin-1 protein. Anomalies in the gene lead to a wide variety of clinical manifestations, including disorders of the cardiac, ocular and musculoskeletal system. We present a case of a child belonging to a Sardinian family of four generations, with a novel variant found in the <jats:italic>FBN1<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To include this novel missense <jats:italic>FBN1<\/jats:italic> variant into genetic counselling for Marfan Syndrome and to discuss its genotypic-phenotypic correlation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Firstly, the proband was diagnosed with Marfan Syndrome using 2020 Revised Ghent Criteria, and she then underwent genetic testing using Next Generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The NGS revealed a novel heterozygous missense variant (c.2348A&amp;gt;G) in the <jats:italic>FBN1<\/jats:italic> gene, in exon 20. This genetic variant caused a missense substitution of a serine residue with an arginine residue in the position 783 of Fibrillin-1 protein. The variant was then evaluated in the other family members, and was eventually only found in symptomatic individuals, regardless of the severity of their phenotype, demonstrating the segregation with MS; furthermore, it showed complete penetrance with the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest that this variant is responsible for MS and it therefore should be included in genetic diagnoses and counselling discussion.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2025.1549504","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T05:29:57Z","timestamp":1741325397000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel missense variant of FBN1 gene in a Sardinian family with Marfan syndrome: a case 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