Unraveling a novel FBN1 variant in Marfan syndrome with dilated aortic root manifestation.

Amirreza Sabahizadeh; Amir Askarinejad; Saranaz Seyed AliAkbar; Mahdieh Soveizi; Golnaz Houshmand; Hojjat Mortezaeian; Amin Elahifar; Majid Maleki; Samira Kalayinia

doi:10.1186/s12920-025-02111-w

PubMed · 40055687

Unraveling a novel FBN1 variant in Marfan syndrome with dilated aortic root manifestation.

Amirreza Sabahizadeh·Amir Askarinejad·Saranaz Seyed AliAkbar·Mahdieh Soveizi·Golnaz Houshmand·Hojjat Mortezaeian·Amin Elahifar·Majid Maleki·Samira Kalayinia

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Abstract

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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Humans Fibrillin-1 Marfan Syndrome Male Adolescent Exome Sequencing Pedigree Aorta Adipokines FBN1 gene Aortic aneurysm Calcium-binding EGF-like domains Marfan syndrome Mitral valve regurgitation Whole-exome sequencing Journal Article Case Reports

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Amirreza Sabahizadeh, Amir Askarinejad, Saranaz Seyed AliAkbar, Mahdieh Soveizi, Golnaz Houshmand, Hojjat Mortezaeian, Amin Elahifar, Majid Maleki, Samira Kalayinia. 2025-03-07. Unraveling a novel FBN1 variant in Marfan syndrome with dilated aortic root manifestation.. https://doi.org/10.1186/s12920-025-02111-w

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