{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:02:02Z","timestamp":1790146922454,"version":"4.0.1"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":264,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["ZL2024H010"],"award-info":[{"award-number":["ZL2024H010"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetics Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by pathogenic variants in the\n                    <jats:italic>FBN1<\/jats:italic>\n                    gene. Using whole\u2010exome sequencing (WES) in a Chinese MFS family, we identified a novel heterozygous nonsense variant\n                    <jats:italic>FBN1<\/jats:italic>\n                    :c.1415dup;p.(Tyr472Ter), which cosegregates with the disease phenotype and results in protein truncation. Immunohistochemical analysis confirmed markedly reduced fibrillin\u20101 expression in the aortic wall of variant carriers, and this variant was classified as pathogenic. Unexpectedly, the proband\u2019s younger sister harbors three independent pathogenic variants responsible for MFS, familial hypercholesterolemia (FH), and oculopharyngeal muscular dystrophy (OPMD). Further transcript validation and functional assays demonstrated that the\n                    <jats:italic>LDLR<\/jats:italic>\n                    :c.1987+1G\u2009&gt;\u2009A;p.Arg662_Gly663insAspLys splice\u2010site mutation generates a stable in\u2010frame insertion transcript, impairing protein structure and function. Supported by robust functional evidence and familial cosegregation, this\n                    <jats:italic>LDLR<\/jats:italic>\n                    variant was upgraded from a variant of uncertain significance to pathogenic. We provided formal genetic counseling, long\u2010term clinical follow\u2010up, and multidisciplinary surveillance to all affected family members, with particularly comprehensive management for the proband\u2019s sister. This study expands the mutational spectrum of\n                    <jats:italic>FBN1<\/jats:italic>\n                    , establishes functional evidence for the pathogenicity of the\n                    <jats:italic>LDLR<\/jats:italic>\n                    variant, and represents the first report of a pediatric individual carrying three coexisting pathogenic variants for rare diseases. Our findings provide critical insights for molecular diagnosis, genetic counseling, and clinical risk stratification in affected families.\n                  <\/jats:p>","DOI":"10.1155\/genr\/7350256","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:21:23Z","timestamp":1790144483000},"source":"Crossref","is-referenced-by-count":0,"title":["A Novel Mutation of the\n                    <i>FBN1<\/i>\n                    Gene in a Chinese Family With Marfan Syndrome and Unanticipated Discoveries of Family 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