{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:16:51Z","timestamp":1790255811943,"version":"4.1.0"},"reference-count":11,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T00:00:00Z","timestamp":1579132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Disease\u2010causing variants in\n                    <jats:italic>TGFB3<\/jats:italic>\n                    cause an autosomal dominant connective tissue disorder which is hard to phenotypically delineate because of the small number of identified cases. The purpose of this retrospective cross\u2010sectional multicenter study is to elucidate the genotype and phenotype in an international cohort of\n                    <jats:italic>TGFB3<\/jats:italic>\n                    patients. Eleven (eight novel)\n                    <jats:italic>TGFB3<\/jats:italic>\n                    disease\u2010causing variants were identified in 32 patients (17 families). Aortic root dilatation and mitral valve disease represented the most common cardiovascular findings, reported in 29% and 32% of patients, respectively. Dissection involving distal aortic segments occurred in two patients at age 50 and 52\u2009years. A high frequency of systemic features (65% high\u2010arched palate, 63% arachnodactyly, 57% pectus deformity, 52% joint hypermobility) was observed. In familial cases, incomplete penetrance and variable clinical expressivity were noted. Our cohort included the first described homozygous patient, who presented with a more severe phenotype compared to her heterozygous relatives. In conclusion,\n                    <jats:italic>TGFB3<\/jats:italic>\n                    variants were associated with a high percentage of systemic features and aortic disease (dilatation\/dissection) in 35% of patients. No deaths occurred from cardiovascular events or pregnancy\u2010related complications. Nevertheless, homozygosity may be driving a more severe phenotype.\n                  <\/jats:p>","DOI":"10.1111\/cge.13700","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T02:31:48Z","timestamp":1578018708000},"page":"723-730","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Phenotypic spectrum of\n                    <i>TGFB3<\/i>\n                    disease\u2010causing variants in a Dutch\u2010French cohort and first report of a homozygous patient"],"prefix":"10.1111","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6691-541X","authenticated-orcid":false,"given":"Luisa","family":"Marsili","sequence":"first","affiliation":[{"name":"Clinique de G\u00e9n\u00e9tique CHU Lille  Lille France"},{"name":"Department of Clinical Genetics, Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline","family":"Overwater","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Clinical Genetics, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Hanna","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Bichat  Paris France"},{"name":"Laboratory for Vascular Translational Science, INSERM U1148 Universit\u00e9 Paris Diderot, H\u00f4pital Bichat  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevi\u00e8ve","family":"Baujat","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique, INSERM U781, H\u00f4pital Necker\u2010Enfants Malades, Institut Imagine University Sorbonne\u2010Paris\u2010Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke J.H.","family":"Baars","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Boileau","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Bichat  Paris France"},{"name":"Laboratory for Vascular Translational Science, INSERM U1148 Universit\u00e9 Paris Diderot, H\u00f4pital Bichat  Paris France"},{"name":"Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Bichat, Facult\u00e9 Paris Diderot, LVTS INSERM U 1148 Centre de R\u00e9f\u00e9rence Pour le Syndrome de Marfan et Apparent\u00e9s  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Bonneau","sequence":"additional","affiliation":[{"name":"Service de g\u00e9n\u00e9tique CHU d'Anger  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Claire","family":"Brehin","sequence":"additional","affiliation":[{"name":"Department of Genetics Normandy Centre for Genomic and Personalized Medicine, Normandie University, UNIROUEN, Inserm U1245 and Rouen University Hospital  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yline","family":"Capri","sequence":"additional","affiliation":[{"name":"Department of Genetics, APHP\u2010Robert DEBRE University Hospital, Denis Diderot School of Medicine Paris University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Y.","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eelco","family":"Dulfer","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Gerard","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique CHU Caen  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Gouya","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Bichat, Facult\u00e9 Paris Diderot, LVTS INSERM U 1148 Centre de R\u00e9f\u00e9rence Pour le Syndrome de Marfan et Apparent\u00e9s  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne","family":"Hilhorst\u2010Hofstee","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan C.","family":"Houweling","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale CHU Nantes  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauriane","family":"Le Gloan","sequence":"additional","affiliation":[{"name":"Clinique Cardiologique et des Maladies Vasculaires CHU Nantes  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie A.","family":"Menke","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Odent","sequence":"additional","affiliation":[{"name":"CHU de Rennes, Service de G\u00e9n\u00e9tique Clinique Universit\u00e9 Rennes, CNRS UMR6290 IGDR (Institut de G\u00e9n\u00e9tique et D\u00e9veloppement de Rennes)  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Morice\u2010Picard","sequence":"additional","affiliation":[{"name":"Service de dermatologie Unit\u00e9 de Dermato\u2010P\u00e9diatrie du CHU de Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3884-2054","authenticated-orcid":false,"given":"Clemence","family":"Vanlerberghe","sequence":"additional","affiliation":[{"name":"Clinique de G\u00e9n\u00e9tique CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Els","family":"Voorhoeve","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Peter","family":"van Tintelen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Genetics, Utrecht University Medical Center Utrecht University  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Maugeri","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam UMC Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9727-1592","authenticated-orcid":false,"given":"Pauline","family":"Arnaud","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique Assistance Publique\u2010H\u00f4pitaux de Paris, H\u00f4pital Bichat  Paris France"},{"name":"Laboratory for Vascular Translational Science, INSERM U1148 Universit\u00e9 Paris Diderot, H\u00f4pital Bichat  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36056"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.63"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.01.040"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13038"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcp.2015.07.003"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36593"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23565"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23407"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2015.04.106"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.04.089"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.13700","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13700","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.13700","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13700","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T22:26:45Z","timestamp":1694039205000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13700"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,16]]},"references-count":11,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1111\/cge.13700"],"URL":"https:\/\/doi.org\/10.1111\/cge.13700","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.13700\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13700\/v2\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13700\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13700\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13700\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13700\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13700\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13700\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13700\/v2\/response1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,16]]},"assertion":[{"value":"2019-10-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}