{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T16:39:47Z","timestamp":1764175187871,"version":"build-2065373602"},"reference-count":75,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"ANID Fondecyt","doi-asserted-by":"publisher","award":["11170353","1171014","1211411","EQM190110","210012","EQM150093"],"award-info":[{"award-number":["11170353","1171014","1211411","EQM190110","210012","EQM150093"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"ANID Fondecyt","doi-asserted-by":"publisher","award":["11170353","1171014","1211411","EQM190110","210012","EQM150093"],"award-info":[{"award-number":["11170353","1171014","1211411","EQM190110","210012","EQM150093"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"ANID","doi-asserted-by":"publisher","award":["11170353","1171014","1211411","EQM190110","210012","EQM150093"],"award-info":[{"award-number":["11170353","1171014","1211411","EQM190110","210012","EQM150093"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ANID ACT","award":["11170353","1171014","1211411","EQM190110","210012","EQM150093"],"award-info":[{"award-number":["11170353","1171014","1211411","EQM190110","210012","EQM150093"]}]},{"name":"Cluster SOFIA-UDD","award":["11170353","1171014","1211411","EQM190110","210012","EQM150093"],"award-info":[{"award-number":["11170353","1171014","1211411","EQM190110","210012","EQM150093"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Marfan Syndrome (MFS) is an autosomal dominant condition caused by variants in the fibrillin-1 (FBN1) gene. Cardinal features of MFS include ectopia lentis (EL), musculoskeletal features and aortic root aneurysm and dissection. Although dissection of the ascending aorta is the main cause of mortality in MFS, the clinical course differs considerably in age of onset and severity, even among individuals who share the same causative variant, suggesting the existence of additional genetic variants that modify the severity of the cardiovascular phenotype in MFS. We recruited MFS patients and classified them into severe (n = 8) or mild aortic phenotype (n = 14) according to age of presentation of the first aorta-related incident. We used Exome Sequencing to identify the genetic variants associated with the severity of aortic manifestations and we performed linkage analysis where suitable. We found five genes associated with severe aortic phenotype and three genes that could be protective for this phenotype in MFS. These genes regulate components of the extracellular matrix, TGF\u03b2 pathway and other signaling pathways that are involved in the maintenance of the ECM or angiogenesis. Further studies will be required to understand the functional effect of these variants and explore novel, personalized risk management and, potentially, therapies for these patients.<\/jats:p>","DOI":"10.3390\/genes13061027","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:22:39Z","timestamp":1654820559000},"page":"1027","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exome Sequencing Identifies Genetic Variants Associated with Extreme Manifestations of the Cardiovascular Phenotype in Marfan Syndrome"],"prefix":"10.3390","volume":"13","author":[{"given":"Yanireth","family":"Jimenez","sequence":"first","affiliation":[{"name":"Doctorado en Ciencias e Innovaci\u00f3n en Medicina, Facultad de Medicina Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 8320000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cesar","family":"Paulsen","sequence":"additional","affiliation":[{"name":"Servicio de Cirug\u00eda Cardiovascular, Instituto Nacional del T\u00f3rax, Santiago 7500808, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Turner","sequence":"additional","affiliation":[{"name":"Servicio de Cirug\u00eda Cardiovascular, Instituto Nacional del T\u00f3rax, Santiago 7500808, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Iturra","sequence":"additional","affiliation":[{"name":"Servicio de Cirug\u00eda Cardiovascular, Instituto Nacional del T\u00f3rax, Santiago 7500808, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Cuevas","sequence":"additional","affiliation":[{"name":"Servicio de Cirug\u00eda Cardiovascular, Instituto Nacional del T\u00f3rax, Santiago 7500808, Chile"},{"name":"Departamento de Cirug\u00eda Cardiovascular, Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 8320000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-1253","authenticated-orcid":false,"given":"Guillermo","family":"Lay-son","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00e9tica, Divisi\u00f3n de Pediatr\u00eda, Facultad de Medicina, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 8331150, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0120-5684","authenticated-orcid":false,"given":"Gabriela M.","family":"Repetto","sequence":"additional","affiliation":[{"name":"Programa de Enfermedades Poco Frecuentes, Centro de Gen\u00e9tica y Gen\u00f3mica, Instituto de Ciencias e Innovaci\u00f3n en Medicina, Facultad de Medicina Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 8320000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1464-2277","authenticated-orcid":false,"given":"Marcelo","family":"Rojas","sequence":"additional","affiliation":[{"name":"Doctorado en Ciencias e Innovaci\u00f3n en Medicina, Facultad de Medicina Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 8320000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2072-704X","authenticated-orcid":false,"given":"Juan F.","family":"Calderon","sequence":"additional","affiliation":[{"name":"Centro de Gen\u00e9tica y Gen\u00f3mica, Instituto de Ciencias e Innovaci\u00f3n en Medicina, Facultad de Medicina Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 8320000, Chile"},{"name":"Research Center for the Development of Novel Therapeutic Alternatives for Alcohol Use Disorders, Santiago 8320000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1136\/jmg.2005.039669","article-title":"The molecular genetics of Marfan syndrome and related disorders","volume":"43","author":"Robinson","year":"2006","journal-title":"J. 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