{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:55:37Z","timestamp":1785819337558,"version":"3.56.0"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Marfan syndrome (MFS) is a complex genetic systemic connective tissue disorder. It is well known that genetic factors play a critical role in the progression of MFS, with nearly all cases attributed to variants in the <jats:italic>FBN1<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated a Chinese family with MFS spanning two generations. Whole exome sequencing, in silico analysis, minigene constructs, transfection, RT\u2010PCR, and protein secondary structure analysis were used to analyze the genotype of the proband and his father.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The main clinical manifestations of the proband and his father were subluxation of the left lens and high myopia with pectus deformity. Whole exome sequencing identified a novel single nucleotide variant (SNV) in the <jats:italic>FBN1<\/jats:italic> gene at a non\u2010canonical splice site, c.443\u20103C&gt;G. This variant resulted in two abnormal mRNA transcripts, leading to a frameshift and an in\u2010frame insertion. Further in\u00a0vitro experiments indicated that the c.443\u20103C&gt;G variant in <jats:italic>FBN1<\/jats:italic> was pathogenic and functionally harmful.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This research identified a novel intronic pathogenic <jats:italic>FBN1<\/jats:italic>: c.443\u20103C&gt;G gene variant, which led to two different aberrant splicing effects. Further functional analysis expands the variant spectrum and provides a strong indication and sufficient basis for preimplantation genetic testing for monogenic disease (PGT\u2010M).<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70004","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T07:48:11Z","timestamp":1725263291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Novel Heterozygous Intronic <scp>FBN1<\/scp> Variant Contributes to Aberrant <scp>RNA<\/scp> Splicing in Marfan Syndrome"],"prefix":"10.1002","volume":"12","author":[{"given":"Djouhayna","family":"Dougarem","sequence":"first","affiliation":[{"name":"School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine Zhejiang University  Hangzhou 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