Three Novel Variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndrome
Abstract Background Marfan syndrome (MFS) is a multi‐systemic autosomal dominant disease of the connective tissue characterized by the early development of thoracic aneurysms/dissections, along with various manifestations of the ocular and skeletal systems. Due to the genetic and clinical heterogene...
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| Format: | Article |
| Language: | English |
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Wiley
2020-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1274 |
| _version_ | 1797301087435227136 |
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| author | Fatemeh Bitarafan Ehsan Razmara Mehrnoosh Khodaeian Mohammad Keramatipour Alireza Kalhor Ehsan Jafarinia Masoud Garshasbi |
| author_facet | Fatemeh Bitarafan Ehsan Razmara Mehrnoosh Khodaeian Mohammad Keramatipour Alireza Kalhor Ehsan Jafarinia Masoud Garshasbi |
| author_sort | Fatemeh Bitarafan |
| collection | DOAJ |
| description | Abstract Background Marfan syndrome (MFS) is a multi‐systemic autosomal dominant disease of the connective tissue characterized by the early development of thoracic aneurysms/dissections, along with various manifestations of the ocular and skeletal systems. Due to the genetic and clinical heterogeneity, the clinical diagnosis of this disorder is challenging. Loss‐of‐function mutations in FBN1 (encodes fibrillin‐1) lead to MFS type 1. Also, similar mutations in transforming growth factor β receptor 2 (TGFBR2) gene cause MFS type 2. Both proteins involve in TGF‐β signaling. Methods In this study, genetic screening using a panel involving 14 genes, especially FBN1 and TGFBR2, were performed on seven representatives affected members of seven unrelated Iranian families suspected with MFS. To confirm the variants, Sanger sequencing was applied to other affected/unaffected members of the families. Results A total of 13 patients showed MFS manifestations. Using genetic screening, two novel and three previously reported variants in FBN1 were identified. We also detected two variants (a novel and a previously reported variant) in the TGFBR2 gene. Conclusion In this study, we introduce three novel variants identified through gene screening in seven Iranian MFS families. This report is expected to considerably improve genetic counseling for Iranian MFS families. Early precise molecular diagnosis can be helpful for better management and improving the life expectancy of these patients. |
| first_indexed | 2024-03-07T23:16:22Z |
| format | Article |
| id | doaj.art-d745eb198f4d48e1bd3298d55047c99d |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T23:16:22Z |
| publishDate | 2020-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-d745eb198f4d48e1bd3298d55047c99d2024-02-21T11:08:50ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-08-0188n/an/a10.1002/mgg3.1274Three Novel Variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndromeFatemeh Bitarafan0Ehsan Razmara1Mehrnoosh Khodaeian2Mohammad Keramatipour3Alireza Kalhor4Ehsan Jafarinia5Masoud Garshasbi6Department of Cellular and Molecular Biology North Tehran Branch Islamic Azad University Tehran IranDepartment of Medical Genetics Faculty of Medical Sciences Tarbiat Modares University Teheran IranDepartment of Medical GeneticsDeNA Laboratory Tehran IranDepartment of Medical Genetics School of Medicine Tehran University of Medical Sciences Tehran IranDepartment of medical science Qom Branch Islamic Azad University Qom IranDepartment of Medical Genetics Faculty of Medical Sciences Tarbiat Modares University Teheran IranDepartment of Medical Genetics Faculty of Medical Sciences Tarbiat Modares University Teheran IranAbstract Background Marfan syndrome (MFS) is a multi‐systemic autosomal dominant disease of the connective tissue characterized by the early development of thoracic aneurysms/dissections, along with various manifestations of the ocular and skeletal systems. Due to the genetic and clinical heterogeneity, the clinical diagnosis of this disorder is challenging. Loss‐of‐function mutations in FBN1 (encodes fibrillin‐1) lead to MFS type 1. Also, similar mutations in transforming growth factor β receptor 2 (TGFBR2) gene cause MFS type 2. Both proteins involve in TGF‐β signaling. Methods In this study, genetic screening using a panel involving 14 genes, especially FBN1 and TGFBR2, were performed on seven representatives affected members of seven unrelated Iranian families suspected with MFS. To confirm the variants, Sanger sequencing was applied to other affected/unaffected members of the families. Results A total of 13 patients showed MFS manifestations. Using genetic screening, two novel and three previously reported variants in FBN1 were identified. We also detected two variants (a novel and a previously reported variant) in the TGFBR2 gene. Conclusion In this study, we introduce three novel variants identified through gene screening in seven Iranian MFS families. This report is expected to considerably improve genetic counseling for Iranian MFS families. Early precise molecular diagnosis can be helpful for better management and improving the life expectancy of these patients.https://doi.org/10.1002/mgg3.1274FBN1Marfan syndromenext‐generation sequencingnovel variantsTGFBR2 |
| spellingShingle | Fatemeh Bitarafan Ehsan Razmara Mehrnoosh Khodaeian Mohammad Keramatipour Alireza Kalhor Ehsan Jafarinia Masoud Garshasbi Three Novel Variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndrome Molecular Genetics & Genomic Medicine FBN1 Marfan syndrome next‐generation sequencing novel variants TGFBR2 |
| title | Three Novel Variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndrome |
| title_full | Three Novel Variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndrome |
| title_fullStr | Three Novel Variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndrome |
| title_full_unstemmed | Three Novel Variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndrome |
| title_short | Three Novel Variants identified in FBN1 and TGFBR2 in seven Iranian families with suspected Marfan syndrome |
| title_sort | three novel variants identified in fbn1 and tgfbr2 in seven iranian families with suspected marfan syndrome |
| topic | FBN1 Marfan syndrome next‐generation sequencing novel variants TGFBR2 |
| url | https://doi.org/10.1002/mgg3.1274 |
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