{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:05:01Z","timestamp":1790193901752,"version":"4.1.0"},"reference-count":28,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine of the National Kapodistrian University of Athens"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Pathogenic variants within the gene encoding transforming growth factor \u03b2 (TGF-\u03b2) are responsible for Loeys-Dietz syndrome (LDS), a heritable thoracic aortic disease sharing clinical features with Marfan syndrome, including craniofacial and skeletal abnormalities as well as aortic root aneurysms and dissections. In contrast to Marfan syndrome patients, who rarely develop aneurysms or dissections beyond the aortic root, LDS patients frequently exhibit vessel aneurysms in locations other than the aortic root. Here, we report the case of a 61-year-old patient who initially presented with marfanoid characteristics and an aortic root aneurysm and was presumed to have Marfan syndrome two decades ago. Later, the patient developed an abdominal aorta aneurysm, necessitating endovascular repair and stent placement. That fact raised doubts regarding the initial diagnosis of Marfan syndrome, and we decided to investigate the genetic cause of the disorder. Methods: Genetic testing was performed using WES analysis and Sanger sequencing. Results: The genetic analysis detected a de novo heterozygous pathogenic variant c.896G&gt;A in exon 5 of the TGFB2 gene, resulting in the amino acid substitution p. Arg299Gln that has devastating destabilizing structural effects on 3D folding of the protein, as demonstrated by the molecular modeling study we performed. This variant is pathogenic for LDS type 4, partially consistent with the patient\u2019s clinical presentation. Conclusions: Our case emphasizes the significance of precise clinical assessment and genetic verification in patients exhibiting marfanoid characteristics. Furthermore, our findings contribute to the understanding of the diverse clinical spectrum associated with this specific pathogenic variant of TGFB2, underscoring the importance of detailed clinical assessment in expanding knowledge of genotype-phenotype correlations. Accurate diagnosis is crucial for tailored and appropriate management of individuals with heritable thoracic aortic diseases.<\/jats:p>","DOI":"10.3390\/genes16040357","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T07:25:00Z","timestamp":1742541900000},"page":"357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genotype-Phenotype Correlation Insights Through Molecular Modeling Analysis in a Patient with Loeys-Dietz Syndrome"],"prefix":"10.3390","volume":"16","author":[{"given":"Galateia","family":"Stathori","sequence":"first","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"},{"name":"Clinical and Translational Research Endocrine Unit, School of Medicine, National Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Koniari","sequence":"additional","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"},{"name":"Clinical and Translational Research Endocrine Unit, School of Medicine, National Kapodistrian University of Athens, 115 28 Athens, Greece"},{"name":"Unit of Orofacial Genetics, 1st Department of Pediatrics, School of Medicine, National Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1823-6102","authenticated-orcid":false,"given":"Dimitrios","family":"Vlachakis","sequence":"additional","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"},{"name":"Laboratory of Genetics, Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 118 55 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Papanikolaou","sequence":"additional","affiliation":[{"name":"Clinical and Translational Research Endocrine Unit, School of Medicine, National Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-5264","authenticated-orcid":false,"given":"George P.","family":"Chrousos","sequence":"additional","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"},{"name":"Clinical and Translational Research Endocrine Unit, School of Medicine, National Kapodistrian University of Athens, 115 28 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6695-186X","authenticated-orcid":false,"given":"Christos","family":"Yapijakis","sequence":"additional","affiliation":[{"name":"University Research Institute of Maternal and Child Health and Precision Medicine, School of Medicine, National Kapodistrian University of Athens, 115 27 Athens, Greece"},{"name":"Unit of Orofacial Genetics, 1st Department of Pediatrics, School of Medicine, National Kapodistrian University of Athens, \u201cAghia Sophia\u201d Children\u2019s Hospital, 115 27 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/ng1511","article-title":"A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2","volume":"37","author":"Loeys","year":"2005","journal-title":"Nat. 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