{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:43:14Z","timestamp":1785775394731,"version":"3.56.0"},"reference-count":6,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T00:00:00Z","timestamp":1701648000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T00:00:00Z","timestamp":1701648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cardiothorac Surg"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The role of\n                      <jats:italic>ACTA2<\/jats:italic>\n                      mutations in Familial Aortic Disease has been increasingly recognized. We describe a highly penetrant variant (R118Q) in a family with aortic disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case report<\/jats:title>\n                    <jats:p>\n                      A patient presented to us for elective repair of an ascending aortic aneurysm with a family history of his mother expiring after aortic dissection. Genetic testing revealed he was a heterozygous carrier of the\n                      <jats:italic>ACTA2<\/jats:italic>\n                      missense mutation R118Q. Subsequently, all living family members were tested for this variant and a full medical history was obtained to compile a family tree for the variant and penetrance of an aortic event (defined as lifetime occurrence of aortic surgery \/ dissection). In total 9 family members were identified and underwent genetic testing with 7\/9 showing presence of the\n                      <jats:italic>ACTA2<\/jats:italic>\n                      R118Q mutation or an aortic event. All patients over the age of 50 (n\u2009=\u20094) had an aortic event. Those events occurred at ages 54, 55, 60, and 62 (mean event at 57.8\u2009\u00b1\u20093.9\u00a0years). Three family members with the variant under the age of 40 have not had an aortic event and most are undergoing regular aortic surveillance via CT scan.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Existing studies of known\n                      <jats:italic>ACTA2<\/jats:italic>\n                      mutations describe a 76% aortic event rate by 85\u00a0years old. The R118Q missense mutation is a less common\n                      <jats:italic>ACTA2<\/jats:italic>\n                      variant, estimated to be found in about 5% of patients with known mutations. Prior studies have predicted the R118Q mutation to have a slightly decreased risk of aortic events compared to other\n                      <jats:italic>ACTA2<\/jats:italic>\n                      mutations. In this family, however, we demonstrate 100% penetrance of aortic disease above age 50. In today\u2019s era of excellent outcomes in elective aortic surgery, our team aggressively offers elective repair. We advocate for strict aortic surveillance for patients with this variant and would consider elective aortic replacement at 4.5\u00a0cm, or at an even smaller diameter in patients with a strong family history of dissection who are identified with this mutation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13019-023-02420-0","type":"journal-article","created":{"date-parts":[[2023,12,3]],"date-time":"2023-12-03T21:01:23Z","timestamp":1701637283000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A highly penetrant ACTA2 mutation of thoracic aortic disease"],"prefix":"10.1186","volume":"18","author":[{"given":"Christopher M.","family":"Bobba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Azarrafiy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Spratt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Hendrickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas D.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George J.","family":"Arnaoutakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric I.","family":"Jeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Beaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,12,4]]},"reference":[{"issue":"4","key":"2420_CR1","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1093\/ejcts\/ezx324","volume":"52","author":"V Falk","year":"2017","unstructured":"Falk V, Baumgartner H, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC\/EACTS guidelines for the management of valvular heart disease. Eur J Cardiothorac Surg. 2017;52(4):616\u201364.","journal-title":"Eur J Cardiothorac Surg"},{"issue":"12","key":"2420_CR2","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1038\/ng.2007.6","volume":"39","author":"DC Guo","year":"2007","unstructured":"Guo DC, Pannu H, Tran-Fadulu V, Papke CL, Yu RK, Avidan N, et al. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007;39(12):1488\u201393.","journal-title":"Nat Genet"},{"issue":"3","key":"2420_CR3","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1161\/CIRCGENETICS.114.000943","volume":"8","author":"ES Regalado","year":"2015","unstructured":"Regalado ES, Guo DC, Prakash S, Bensend TA, Flynn K, Estrera A, et al. Aortic disease presentation and outcome associated with ACTA2 mutations. Circ Cardiovasc Genet. 2015;8(3):457\u201364.","journal-title":"Circ Cardiovasc Genet"},{"issue":"2","key":"2420_CR4","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/j.athoracsur.2016.06.007","volume":"103","author":"AS Chou","year":"2017","unstructured":"Chou AS, Ma WG, Mok SC, Ziganshin BA, Peterss S, Rizzo JA, Tranquilli M, et al. Do familial aortic dissections tend to occur at the same age? Ann Thorac Surg. 2017;103(2):546\u201350.","journal-title":"Ann Thorac Surg"},{"issue":"1","key":"2420_CR5","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jtcvs.2018.07.114","volume":"157","author":"BA Ziganshin","year":"2019","unstructured":"Ziganshin BA, Zafar MA, Elefteriades JA. Descending threshold for ascending aortic aneurysmectomy: is it time for a \u201cleft-shift\u201d in guidelines? J Thorac Cardiovasc Surg. 2019;157(1):37\u201342.","journal-title":"J Thorac Cardiovasc Surg"},{"issue":"24","key":"2420_CR6","doi-asserted-by":"publisher","first-page":"e334","DOI":"10.1161\/CIR.0000000000001106","volume":"146","author":"EM Isselbacher","year":"2022","unstructured":"Isselbacher EM, Preventza O, Hamilton Black J, Augoustides JG, Beck AW, Bolen MA, et al. ACC\/AHA guideline for the diagnosis and management of aortic disease: a report of the American Heart Association\/American College of Cardiology joint committee on clinical practice guidelines. Circulation. 2022;146(24):e334\u2013482.","journal-title":"Circulation"}],"container-title":["Journal of Cardiothoracic Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13019-023-02420-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13019-023-02420-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13019-023-02420-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T09:07:28Z","timestamp":1701680848000},"score":1,"resource":{"primary":{"URL":"https:\/\/cardiothoracicsurgery.biomedcentral.com\/articles\/10.1186\/s13019-023-02420-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,4]]},"references-count":6,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["2420"],"URL":"https:\/\/doi.org\/10.1186\/s13019-023-02420-0","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2476466\/v1","asserted-by":"object"}]},"ISSN":["1749-8090"],"issn-type":[{"value":"1749-8090","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,4]]},"assertion":[{"value":"13 January 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 December 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The University of Florida does not require IRB approval for case reports. Written informed consent was obtained for publication of de-identified medical information from each family member, with documentation available upon request. Permission was granted from the family for publication of this de-identified case-report. Details of the proband\u2019s operation and hospital course was obtained from chart review.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Informed consent for publication of this family pedigree and details of the proband\u2019s operation and hospital course was granted by the family, with documentation available upon request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"352"}}