Genetic insights from a Brazilian cohort of aortopathies through targeted next-generation sequencing and FBN1 direct sequencing
Abstract Thoracic aortic diseases (or aortopathies) result from complex interactions between genetic and hemodynamic factors. Often clinically silent, these diseases can lead to lethal complications such as aortic dissection or rupture. This study focused on a Brazilian cohort of 79 individuals with...
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Nature Portfolio
2024-11-01
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| Online Access: | https://doi.org/10.1038/s41598-024-78788-3 |
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| author | Juliana Rocha Ferreira Julia Passarelli Pereira Anna Paula Arpini Botelho Daniele do Nascimento Aprijo Marcelo Machado Melo Helena Cramer Veiga Rey Glauber Monteiro Dias |
| author_facet | Juliana Rocha Ferreira Julia Passarelli Pereira Anna Paula Arpini Botelho Daniele do Nascimento Aprijo Marcelo Machado Melo Helena Cramer Veiga Rey Glauber Monteiro Dias |
| author_sort | Juliana Rocha Ferreira |
| collection | DOAJ |
| description | Abstract Thoracic aortic diseases (or aortopathies) result from complex interactions between genetic and hemodynamic factors. Often clinically silent, these diseases can lead to lethal complications such as aortic dissection or rupture. This study focused on a Brazilian cohort of 79 individuals with thoracic aortic diseases and explored genetic factors through targeted next-generation sequencing (tNGS) of 15 priority genes and FBN1 direct sequencing. The majority of individuals had nonsyndromic aortopathy, with eight diagnosed with Marfan syndrome (MFS). Pathogenic or likely pathogenic variants (PV/LPV) were found in five genes, namely, FBN1, ACTA2, TGFBR2, MYLK, and SMAD3. Notably, novel variants in FBN1 were identified that contributed to Marfan-like phenotypes. The diagnostic yield for isolated aortopathies was 7.1%, which increased to 55.5% for syndromic cases. Variants of uncertain significance (VUS) were identified, emphasizing the need for further research and familial investigations to refine variant classifications. This study provides valuable insights into the genetic landscape of aortopathies in Brazil, aiding early diagnosis and personalized management. |
| format | Article |
| id | doaj-art-20c21131edc8482783c292e48c3b8ba4 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-20c21131edc8482783c292e48c3b8ba42024-11-10T12:20:57ZengNature PortfolioScientific Reports2045-23222024-11-0114111110.1038/s41598-024-78788-3Genetic insights from a Brazilian cohort of aortopathies through targeted next-generation sequencing and FBN1 direct sequencingJuliana Rocha Ferreira0Julia Passarelli Pereira1Anna Paula Arpini Botelho2Daniele do Nascimento Aprijo3Marcelo Machado Melo4Helena Cramer Veiga Rey5Glauber Monteiro Dias6National Institute of CardiologyNational Institute of CardiologyNational Institute of CardiologyNational Institute of CardiologyNational Institute of CardiologyNational Institute of CardiologyCellular and Tissue Biology Laboratory, State University of Norte Fluminense Darcy RibeiroAbstract Thoracic aortic diseases (or aortopathies) result from complex interactions between genetic and hemodynamic factors. Often clinically silent, these diseases can lead to lethal complications such as aortic dissection or rupture. This study focused on a Brazilian cohort of 79 individuals with thoracic aortic diseases and explored genetic factors through targeted next-generation sequencing (tNGS) of 15 priority genes and FBN1 direct sequencing. The majority of individuals had nonsyndromic aortopathy, with eight diagnosed with Marfan syndrome (MFS). Pathogenic or likely pathogenic variants (PV/LPV) were found in five genes, namely, FBN1, ACTA2, TGFBR2, MYLK, and SMAD3. Notably, novel variants in FBN1 were identified that contributed to Marfan-like phenotypes. The diagnostic yield for isolated aortopathies was 7.1%, which increased to 55.5% for syndromic cases. Variants of uncertain significance (VUS) were identified, emphasizing the need for further research and familial investigations to refine variant classifications. This study provides valuable insights into the genetic landscape of aortopathies in Brazil, aiding early diagnosis and personalized management.https://doi.org/10.1038/s41598-024-78788-3Thoracic aortic diseaseAortic aneurysm and dissectionMarfan syndromeGenetic variant pathogenicityNext-generation sequencing |
| spellingShingle | Juliana Rocha Ferreira Julia Passarelli Pereira Anna Paula Arpini Botelho Daniele do Nascimento Aprijo Marcelo Machado Melo Helena Cramer Veiga Rey Glauber Monteiro Dias Genetic insights from a Brazilian cohort of aortopathies through targeted next-generation sequencing and FBN1 direct sequencing Scientific Reports Thoracic aortic disease Aortic aneurysm and dissection Marfan syndrome Genetic variant pathogenicity Next-generation sequencing |
| title | Genetic insights from a Brazilian cohort of aortopathies through targeted next-generation sequencing and FBN1 direct sequencing |
| title_full | Genetic insights from a Brazilian cohort of aortopathies through targeted next-generation sequencing and FBN1 direct sequencing |
| title_fullStr | Genetic insights from a Brazilian cohort of aortopathies through targeted next-generation sequencing and FBN1 direct sequencing |
| title_full_unstemmed | Genetic insights from a Brazilian cohort of aortopathies through targeted next-generation sequencing and FBN1 direct sequencing |
| title_short | Genetic insights from a Brazilian cohort of aortopathies through targeted next-generation sequencing and FBN1 direct sequencing |
| title_sort | genetic insights from a brazilian cohort of aortopathies through targeted next generation sequencing and fbn1 direct sequencing |
| topic | Thoracic aortic disease Aortic aneurysm and dissection Marfan syndrome Genetic variant pathogenicity Next-generation sequencing |
| url | https://doi.org/10.1038/s41598-024-78788-3 |
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