{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T16:30:00Z","timestamp":1793464200869,"version":"4.5.0"},"reference-count":28,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Access Publishing Fund of the Philipps University of Marburg"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objective: To investigate the prevalence and effects of genetic variants (GVs) in survivors of thoracic aortic dissection\/aneurysm repair. Methods: Patients aged 18\u201380 years who survived follow-up after cardiosurgical or endovascular repair of thoracic aortic aneurysm or dissection at a single tertiary center between 2008 and 2019 and underwent genetic testing were enrolled. The exclusion criteria were age &gt;60 years, no offspring, and inflammatory- or trauma-related pathogenesis. Follow-up entailed computed tomography-angiography at 3 and 9 months and annually thereafter. All patients underwent genetic analyses of nine genes using next-generation sequencing. In cases of specific suspicion, the analysis was expanded to include 32 genes. Results: The study included 95 patients. The follow-up period was 3 \u00b1 2.5 years. GVs were detected in 40% of patients. Correlation analysis according to primary diagnosis showed no significant correlation in disease persistence, progression, or in reintervention rates in aneurysm patients and a correlation of disease persistence with genetic variants according to variant class in dissection patients (p = 0.037). Correlation analysis according to follow-up CD finding revealed that patients with detected dissection, irrespective of original pathology, showed a strong correlation with genetic variants regarding disease progression and reintervention rates (p = 0.012 and p = 0.047, respectively). Conclusions: The prevalence of VUS is high in patients with aortic pathology. In patients with dissected aorta in the follow-up, irrespective of original pathology, genetic variants correlate with higher reintervention rates, warranting extended-spectrum genetic testing. The role of VUS may be greater than is currently known.<\/jats:p>","DOI":"10.3390\/jcm13175254","type":"journal-article","created":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T04:15:11Z","timestamp":1725509711000},"page":"5254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prevalence and Influence of Genetic Variants on Follow-Up Results in Patients Surviving Thoracic Aortic Therapy"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2413-4065","authenticated-orcid":false,"given":"Tamer","family":"Ghazy","sequence":"first","affiliation":[{"name":"Department of Cardiac and Thoracic-Vascular Surgery, University Hospital Giessen and Marburg, Philipps University of Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nesma","family":"Elzanaty","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Tanta Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0159-3720","authenticated-orcid":false,"given":"Helmut","family":"Lackner","sequence":"additional","affiliation":[{"name":"Division of Physiology, Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Irqsusi","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Thoracic-Vascular Surgery, University Hospital Giessen and Marburg, Philipps University of Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ardawan","family":"Rastan","sequence":"additional","affiliation":[{"name":"Department of Cardiac and Thoracic-Vascular Surgery, University Hospital Giessen and Marburg, Philipps University of Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0406-3319","authenticated-orcid":false,"given":"Christian-Alexander","family":"Behrendt","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery, Asklepios Clinic Wandsbek, Asklepios Medical School, 20043 Hamburg, Germany"},{"name":"Brandenburg Medical School Theodor Fontane, 16816 Neuruppin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Mahlmann","sequence":"additional","affiliation":[{"name":"Centre for Vascular Medicine, Clinic of Angiology, St.-Josefs-Hospital, Katholische Krankenhaus Hagen gem. GmbH, 58099 Hagen, Germany"},{"name":"Department of Internal Medicine III, University Hospital Carl Gustav Carus at Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1152\/ajpheart.00621.2019","article-title":"Pathogenic mechanisms and the potential of drug therapies for aortic aneurysm","volume":"318","author":"Liu","year":"2020","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11748-017-0874-x","article-title":"Thoracic aortic aneurysm: Unlocking the \u201csilent killer\u201d secrets","volume":"67","author":"Saeyeldin","year":"2019","journal-title":"Gen. Thorac. Cardiovasc. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.carpath.2015.05.001","article-title":"Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology: I. Inflammatory diseases","volume":"24","author":"Stone","year":"2015","journal-title":"Cardiovasc. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e1132","DOI":"10.1002\/mgg3.1132","article-title":"Clinical and genetic data of 22 new patients with SMAD3 pathogenic variants and review of the literature","volume":"8","author":"Chesneau","year":"2020","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1055\/s-0039-3400233","article-title":"Genes Associated with Thoracic Aortic Aneurysm and Dissection: 2019 Update and Clinical Implications","volume":"7","author":"Vinholo","year":"2019","journal-title":"Aorta"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1161\/CIRCRESAHA.118.312436","article-title":"Genetics of thoracic and abdominal aortic diseases","volume":"124","author":"Pinard","year":"2019","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1038\/s41436-019-0435-z","article-title":"Next-generation sequencing of 32 genes associated with hereditary aortopathies and related disorders of connective tissue in a cohort of 199 patients","volume":"21","author":"Renner","year":"2019","journal-title":"Genet. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1093\/hmg\/ddz024","article-title":"Bi-allelic AEBP1 mutations in two patients with Ehlers\u2013Danlos syndrome","volume":"28","author":"Syx","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Takeda, N., Hara, H., Fujiwara, T., Kanaya, T., Maemura, S., and Komuro, I. (2018). TGF-\u03b2 Signaling-Related Genes and Thoracic Aortic Aneurysms and Dissections. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072125"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1038\/gim.2018.27","article-title":"Targeted genetic analysis in a large cohort of familial and sporadic cases of aneurysm or dissection of the thoracic aorta","volume":"20","author":"Weerakkody","year":"2018","journal-title":"Genet. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1002\/humu.20880","article-title":"Sequence variant classification and reporting: Recommendations for improving the interpretation of cancer susceptibility genetic test results","volume":"29","author":"Plon","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1007\/s00246-020-02307-0","article-title":"New Screening Tool for Aortic Root Dilation in Children with Marfan Syndrome and Marfan-Like Disorders","volume":"41","author":"Sabiniewicz","year":"2020","journal-title":"Pediatr. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3949\/ccjm.85a.17039","article-title":"Thoracic aortic aneurysm: How to counsel, when to refer","volume":"85","author":"Cikach","year":"2018","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s12967-016-0870-4","article-title":"Next-generation sequencing for diagnosis of thoracic aortic aneurysms and dissections: Diagnostic yield, novel mutations and genotype phenotype correlations","volume":"14","author":"Poninska","year":"2016","journal-title":"J. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"662","DOI":"10.21037\/acs.2017.09.14","article-title":"Re-interventions on the thoracic and thoracoabdominal aorta in patients with Marfan syndrome","volume":"6","author":"Schoenhoff","year":"2017","journal-title":"Ann. Cardiothorac. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ajhg.2014.11.015","article-title":"MAT2A mutations predispose individuals to thoracic aortic aneurysms","volume":"96","author":"Guo","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1248\/bpb.b18-01012","article-title":"Nox1 negatively modulates fibulin-5 in vascular smooth muscle cells to affect aortic dissection","volume":"42","author":"Hu","year":"2019","journal-title":"Biol. Pharm. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5173","DOI":"10.18632\/aging.102111","article-title":"Genetic polymorphisms and transcription profiles associated with intracranial aneurysm: A key role for NOTCH3","volume":"11","author":"Li","year":"2019","journal-title":"Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1161\/CIRCGENETICS.114.000943","article-title":"Aortic disease presentation and outcome associated with ACTA2 mutations","volume":"8","author":"Regalado","year":"2015","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Fang, M., Yu, C., Chen, S., Xiong, W., Li, X., Zeng, R., Zhuang, J., and Fan, R. (2017). Identification of Novel Clinically Relevant Variants in 70 Southern Chinese patients with Thoracic Aortic Aneurysm and Dissection by Next-generation Sequencing. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09785-y"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/j.athoracsur.2015.04.106","article-title":"Routine genetic testing for thoracic aortic aneurysm and dissection in a clinical setting","volume":"100","author":"Ziganshin","year":"2015","journal-title":"Ann. Thorac. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1800","DOI":"10.1002\/mgg3.1800","article-title":"Genetic testing and clinical relevance of patients with thoracic aortic aneurysm and dissection in northwestern China","volume":"9","author":"Li","year":"2021","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_23","first-page":"4281","article-title":"Analysis of the contribution of 129 candidate genes to thoracic aortic aneurysm or dissection of a mixed cohort of sporadic and familial cases in South China","volume":"13","author":"Li","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ostberg, N., Zafar, M., Ziganshin, B., and Elefteriades, J. (2020). The Genetics of Thoracic aortic aneurysms and Dissection: A Clinical perspective. Biomolecules, 10.","DOI":"10.3390\/biom10020182"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1055\/s-0038-1639612","article-title":"Genes Associated with Thoracic Aortic Aneurysm and Dissection: 2018 Update and Clinical Implications","volume":"6","author":"Brownstein","year":"2018","journal-title":"Aorta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"104673","DOI":"10.1016\/j.ejmg.2022.104673","article-title":"HTAD patient pathway: Strategy for diagnostic work-up of patients and families with (suspected) heritable thoracic aortic diseases (HTAD). A statement from the HTAD working group of VASCERN","volume":"66","author":"Caruana","year":"2023","journal-title":"Eur. J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"ezad426","DOI":"10.1093\/ejcts\/ezad426","article-title":"EACTS\/STS Guidelines for Diagnosing and Treating Acute and Chronic Syndromes of the Aortic Organ","volume":"65","author":"Czerny","year":"2024","journal-title":"Eur. J. Cardio-Thorac. Surg."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mahlmann, A., Elzanaty, N., Saleh, M., Irqsusi, M., Rastan, A., Leip, J.L., Behrendt, C.-A., and Ghazy, T. (2024). Prevalence of Genetic Variants and Deep Phenotyping in Patients with Thoracic Aortic Aneurysm and Dissection: A Cross-Sectional Single-Centre Cohort Study. J. Clin. Med., 13.","DOI":"10.3390\/jcm13020461"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/17\/5254\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:48:54Z","timestamp":1760111334000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/17\/5254"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,5]]},"references-count":28,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["jcm13175254"],"URL":"https:\/\/doi.org\/10.3390\/jcm13175254","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,5]]}}}