Background: Marfan syndrome (MFS) is a genetic disorder affecting connective tissue, with variable incidence rates. A significant portion of cases stems from novel genetic variants, while others inherit it from affected parents.
Objective: This study focuses on identifying the genetic cause of MFS in a specific family, using whole-exome sequencing (WES).
Methods: A 15-year-old male with confirmed MFS was examined, showing symptoms of palpitations and severe mitral valve regurgitation. WES was performed, followed by confirmation with Sanger sequencing. Variants were assessed for pathogenicity using bioinformatics tools and the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results: One potentially novel pathogenic variant was found in exon 14 of the FBN1 gene: c.1676delCinsAAT, p.Ala559GlufsTer21. In silico analysis suggested a deleterious impact on protein structure and function, supporting their pathogenic classification.
Conclusion: The identification of this novel variant highlights the importance of the FBN1 gene in MFS, especially its cardiovascular manifestations. Early intervention can improve patient outcomes, while ongoing research holds promise for further advancements in treatment for Marfan syndrome.
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http://dx.doi.org/10.1186/s12920-025-02111-w | DOI Listing |
Clin Genet
March 2025
Department of Pediatrics, Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Amsterdam, the Netherlands.
Early-onset Marfan syndrome (eoMFS) is a severe and rare form of Marfan syndrome characterized by severe atrioventricular valve insufficiency developing before or shortly after birth. It is unclear which factors (interventions and/or genotype) influence survival. Forty-one individuals with eoMFS with a fibrillin-1 gene (FBN1) variant in exon 24-32 (CRCh37) were included.
View Article and Find Full Text PDFJ Gen Physiol
May 2025
Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
Marfan syndrome (MFS) is an autosomal dominant disease caused by mutations in the gene (FBN1) of fibrillin-1, a major determinant of the extracellular matrix (ECM). Functional impairment in the cardiac left ventricle (LV) of these patients is usually a consequence of aortic valve disease. However, LV passive stiffness may also be affected by chronic changes in mechanical load and ECM dysfunction.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
March 2025
Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China.
Background: We investigated the corneal biomechanical properties and their genotype-phenotype correlation correlations in patients with Marfan syndrome (MFS) and ectopia lentis (EL).
Methods: Patients with MFS with EL underwent panel-based next-generation sequencing in this retrospective cohort study. The FBN1 genotypes were categorized into the dominant-negative (DN) group and the haploinsufficiency (HI) group.
Int J Rheum Dis
March 2025
Department of Rheumatology and Immunology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Purpose Phenotype-based ascertainment of probands in studies of Mendelian disorders may exclude individuals with mild phenotypes or that lack health care access. We explore this premise in All of Us Research Program participants with pathogenic variation causal for three Mendelian conditions: autosomal dominant polycystic kidney disease (ADPKD), Marfan syndrome, and neurofibromatosis type 1 (NF1). Methods We identified All of Us Research Program participants with putatively pathogenic variation in NF1, FBN1, PKD1, and PKD2.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!