{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:42:13Z","timestamp":1792820533327,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008057","name":"Fundaci\u00f3n para la Investigaci\u00f3n del Hospital Universitari La Fe","doi-asserted-by":"publisher","award":["2016\/0114"],"award-info":[{"award-number":["2016\/0114"]}],"id":[{"id":"10.13039\/100008057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI19\/00245"],"award-info":[{"award-number":["PI19\/00245"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RETICS Program RD16\/0011\/0004"],"award-info":[{"award-number":["RETICS Program RD16\/0011\/0004"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Marfan syndrome (MFS) is a systemic connective tissue disorder caused by mutations in the fibrillin\u20101 (\n                    <jats:italic>FBN1<\/jats:italic>\n                    ) gene, and cardiovascular involvement is the leading cause of mortality. We sought to examine the genotype\/phenotype realtionship in 61 consecutive patients with a phenotype and genotype compatible with MFS. The\n                    <jats:italic>FBN1<\/jats:italic>\n                    gene was analyzed by massive sequencing using a hybridization capture\u2010based target enrichment custom panel. Forty\u2010three different variants of\n                    <jats:italic>FBN1<\/jats:italic>\n                    were identified, of which 17 have not been previously reported. The causal variants of MFS were grouped into mutations resulting in haploinsufficiency (HI group; 23 patients) and mutations producing a dominant\u2010negative effect (DN group; 38 patients). Patient information was collected from electronic medical records and clinical evaluation. While no significant differences were found between the two groups, the HI group included more cases with aortic dissection and occurring at a younger age that the DN group (34.7% vs. 15.8%;\n                    <jats:italic>p<\/jats:italic>\n                    = 0.160). Irrespective of the mutation group, males presented with a higher probability of aortic involvement (4\u2010fold higher risk than females) and aortic dissections events occurred at younger ages. Patients with DN variants carrying a cysteine substitution had a higher incidence of\n                    <jats:italic>ectopia lentis<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1111\/cge.13879","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T09:01:31Z","timestamp":1605085291000},"page":"269-280","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Genotype\n                    <scp>\n                      <i>FBN1<\/i>\n                    <\/scp>\n                    \/phenotype relationship in a cohort of patients with Marfan syndrome"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3236-1997","authenticated-orcid":false,"given":"Amparo","family":"Hern\u00e1ndiz","sequence":"first","affiliation":[{"name":"Unidad de Regeneraci\u00f3n y Trasplante card\u00edaco Instituto de Investigaci\u00f3n Sanitaria La Fe  Valencia Espa\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Z\u00fa\u00f1iga","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00e9tica, Hospital Universitario La Fe  Valencia Espa\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Valera","sequence":"additional","affiliation":[{"name":"Servicio de Cirug\u00eda Cardiaca Hospital Universitario La Fe  Valencia Espa\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Domingo","sequence":"additional","affiliation":[{"name":"Servicio de Cardiolog\u00eda Hospital Universitario La Fe  Valencia Espa\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2497-1325","authenticated-orcid":false,"given":"Imelda","family":"Ontoria\u2010Oviedo","sequence":"additional","affiliation":[{"name":"Unidad de Regeneraci\u00f3n y Trasplante card\u00edaco Instituto de Investigaci\u00f3n Sanitaria La Fe  Valencia Espa\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose F.","family":"Mar\u00ed","sequence":"additional","affiliation":[{"name":"Servicio de Oftalmolog\u00eda Hospital Universitario La Fe  Valencia Espa\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Rom\u00e1n","sequence":"additional","affiliation":[{"name":"Servicio de Reumatolog\u00eda Hospital Universitario La Fe  Valencia Espa\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Calvo","sequence":"additional","affiliation":[{"name":"Servicio de Reumatolog\u00eda Pedi\u00e1trica Hospital Universitario La Fe  Valencia Espa\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Insa","sequence":"additional","affiliation":[{"name":"Servicio de Cardiolog\u00eda Pedi\u00e1trica Hospital Universitario La Fe  Valencia Espa\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Servicio de Ginecolog\u00eda, Unidad de Reproducci\u00f3n, Servicio de Ginecolog\u00eda, Hospital Universitario La Fe  Valencia Espa\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 V.","family":"Cervera","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00e9tica, Hospital Universitario La Fe  Valencia Espa\u00f1a Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Miralles","sequence":"additional","affiliation":[{"name":"Servicio de Angiolog\u00eda y Cirug\u00eda Vascular Hospital Universitario La Fe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Montero","sequence":"additional","affiliation":[{"name":"Unidad de Regeneraci\u00f3n y Trasplante card\u00edaco Instituto de 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