Clinical and genetic screening in a large Iranian family with Marfan syndrome: A case study
Abstract Background and Aims Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by pathogenic variants of the fibrillin‐1‐encoding FBN1 gene that commonly affects the cardiovascular, skeletal, and ocular systems. This study aimed to evaluate the clinical features and genetic caus...
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| Format: | Article |
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Wiley
2023-10-01
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| Series: | Health Science Reports |
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| Online Access: | https://doi.org/10.1002/hsr2.1647 |
| _version_ | 1797310536795291648 |
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| author | Farzane Vafaeie Zahra Miri Karam Abolfazl Yari Hossein Safarpour Tooba Kazemi Shokoofeh Etesam Mojtaba Mohammadpour Ebrahim Miri‐Moghaddam |
| author_facet | Farzane Vafaeie Zahra Miri Karam Abolfazl Yari Hossein Safarpour Tooba Kazemi Shokoofeh Etesam Mojtaba Mohammadpour Ebrahim Miri‐Moghaddam |
| author_sort | Farzane Vafaeie |
| collection | DOAJ |
| description | Abstract Background and Aims Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by pathogenic variants of the fibrillin‐1‐encoding FBN1 gene that commonly affects the cardiovascular, skeletal, and ocular systems. This study aimed to evaluate the clinical features and genetic causes of the MFS phenotype in a large Iranian family. Methods Seventeen affected family members were examined clinically by cardiologists and ophthalmologists. The proband, a 48‐year‐old woman with obvious signs of MFS, her DNA sample subjected to whole‐exome sequencing (WES). The candidate variant was validated by bidirectional sequencing of proband and other available family members. In silico analysis and molecular modeling were conducted to determine the pathogenic effects of the candidate variants. Results The most frequent cardiac complications are mitral valve prolapse and regurgitation. Ophthalmic examination revealed iridodonesis and ectopic lentis. A heterozygous missense variant (c.2179T>C/p.C727R) in exon 19 of FBN1 gene was identified and found to cosegregate with affected family members. Its pathogenicity has been predicted using several in silico predictive algorithms. Molecular docking analysis indicated that the variant might affect the binding affinity between FBN1 and LTBP1 proteins by impairing disulfide bond formation. Conclusion Our report expands the spectrum of the Marfan phenotype by providing details of its clinical manifestations and disease‐associated molecular changes. It also highlights the value of WES in genetic diagnosis and contributes to genetic counseling in families with MFS. |
| first_indexed | 2024-03-08T01:45:23Z |
| format | Article |
| id | doaj.art-96a888b148644dbbae8b6863192e6fac |
| institution | Directory Open Access Journal |
| issn | 2398-8835 |
| language | English |
| last_indexed | 2024-03-08T01:45:23Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Health Science Reports |
| spelling | doaj.art-96a888b148644dbbae8b6863192e6fac2024-02-14T13:06:23ZengWileyHealth Science Reports2398-88352023-10-01610n/an/a10.1002/hsr2.1647Clinical and genetic screening in a large Iranian family with Marfan syndrome: A case studyFarzane Vafaeie0Zahra Miri Karam1Abolfazl Yari2Hossein Safarpour3Tooba Kazemi4Shokoofeh Etesam5Mojtaba Mohammadpour6Ebrahim Miri‐Moghaddam7Cellular and Molecular Research Center Birjand University of Medical Sciences Birjand IranPhysiology Research Center, Institute of Neuropharmacology Kerman University of Medical Sciences Kerman IranCellular and Molecular Research Center Birjand University of Medical Sciences Birjand IranCellular and Molecular Research Center Birjand University of Medical Sciences Birjand IranCardiovascular Disease Research Center, Razi Hospital Birjand University of Medical Sciences Birjand IranDepartment of Biological Sciences Technical and Vocational University (TVU) Tehran IranDepartment of Optometry, School of Rehabilitation Shahid Beheshti University of Medical Sciences Tehran IranCardiovascular Disease Research Center, Razi Hospital Birjand University of Medical Sciences Birjand IranAbstract Background and Aims Marfan syndrome (MFS) is an autosomal dominant genetic disorder caused by pathogenic variants of the fibrillin‐1‐encoding FBN1 gene that commonly affects the cardiovascular, skeletal, and ocular systems. This study aimed to evaluate the clinical features and genetic causes of the MFS phenotype in a large Iranian family. Methods Seventeen affected family members were examined clinically by cardiologists and ophthalmologists. The proband, a 48‐year‐old woman with obvious signs of MFS, her DNA sample subjected to whole‐exome sequencing (WES). The candidate variant was validated by bidirectional sequencing of proband and other available family members. In silico analysis and molecular modeling were conducted to determine the pathogenic effects of the candidate variants. Results The most frequent cardiac complications are mitral valve prolapse and regurgitation. Ophthalmic examination revealed iridodonesis and ectopic lentis. A heterozygous missense variant (c.2179T>C/p.C727R) in exon 19 of FBN1 gene was identified and found to cosegregate with affected family members. Its pathogenicity has been predicted using several in silico predictive algorithms. Molecular docking analysis indicated that the variant might affect the binding affinity between FBN1 and LTBP1 proteins by impairing disulfide bond formation. Conclusion Our report expands the spectrum of the Marfan phenotype by providing details of its clinical manifestations and disease‐associated molecular changes. It also highlights the value of WES in genetic diagnosis and contributes to genetic counseling in families with MFS.https://doi.org/10.1002/hsr2.1647FBN1Marfan syndromemolecular dockingpathogenic variantwhole exome sequence |
| spellingShingle | Farzane Vafaeie Zahra Miri Karam Abolfazl Yari Hossein Safarpour Tooba Kazemi Shokoofeh Etesam Mojtaba Mohammadpour Ebrahim Miri‐Moghaddam Clinical and genetic screening in a large Iranian family with Marfan syndrome: A case study Health Science Reports FBN1 Marfan syndrome molecular docking pathogenic variant whole exome sequence |
| title | Clinical and genetic screening in a large Iranian family with Marfan syndrome: A case study |
| title_full | Clinical and genetic screening in a large Iranian family with Marfan syndrome: A case study |
| title_fullStr | Clinical and genetic screening in a large Iranian family with Marfan syndrome: A case study |
| title_full_unstemmed | Clinical and genetic screening in a large Iranian family with Marfan syndrome: A case study |
| title_short | Clinical and genetic screening in a large Iranian family with Marfan syndrome: A case study |
| title_sort | clinical and genetic screening in a large iranian family with marfan syndrome a case study |
| topic | FBN1 Marfan syndrome molecular docking pathogenic variant whole exome sequence |
| url | https://doi.org/10.1002/hsr2.1647 |
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