{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:27:14Z","timestamp":1791296834665,"version":"4.1.0"},"reference-count":22,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T00:00:00Z","timestamp":1549843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DHU Fire","award":["Emergence 2 project"],"award-info":[{"award-number":["Emergence 2 project"]}]},{"name":"Programme Hospitalier de Recherche Clinique (PHRC)","award":["AOM10108, CRC15014"],"award-info":[{"award-number":["AOM10108, CRC15014"]}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-14-CE15-0012-01"],"award-info":[{"award-number":["ANR-14-CE15-0012-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Marfan syndrome (MFS) is a rare connective tissue disorder mainly due to mutations in the FBN1 gene. Great phenotypic variability is notable for age of onset, the presence and absence, and the number and the severity of the symptoms. Our team showed that FBN1 gene expression level was a good surrogate endpoint for severity of some MFS clinical features. Eight alternative transcripts are referenced for the FBN1 gene. We hypothesized that MFS clinical variability could be related to specific FBN1 isoforms. Isoform expression profiles were investigated in skin and adventitial fibroblasts from controls and MFS patients. The results of the study showed that, in skin and adventitial fibroblasts, only three isoforms were found: FBN1_001, FBN1_004, and FBN1_009. The main isoform was FBN1_001 and it was significantly reduced in skin and adventitial fibroblasts of MFS patients. The expressions of FBN1_004 and FBN1_009 isoforms were similar between controls and MFS patients. However, the expression of the three isoforms was correlated only in patients. Furthermore, their expression levels were associated with the presence of ectopia lentis in MFS patients. Therefore, our results highlight that the two minor alternatively spliced FBN1 isoforms play a possible role in the pathogenesis of the disease.<\/jats:p>","DOI":"10.3390\/genes10020128","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T03:18:20Z","timestamp":1549941500000},"page":"128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Reference Expression Profile of Three FBN1 Transcript Isoforms and Their Association with Clinical Variability in Marfan Syndrome"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2805-9170","authenticated-orcid":false,"given":"Louise","family":"Benarroch","sequence":"first","affiliation":[{"name":"Laboratory for Vascular Translational Science, INSERM U1148, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri Huchard, 75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lodie","family":"Aubart","sequence":"additional","affiliation":[{"name":"Laboratory for Vascular Translational Science, INSERM U1148, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri Huchard, 75018 Paris, France"},{"name":"Service de Neurop\u00e9diatrie, H\u00f4pital Necker-Enfants-Malades, 149 rue de S\u00e8vres, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Sylvie","family":"Gross","sequence":"additional","affiliation":[{"name":"Laboratory for Vascular Translational Science, INSERM U1148, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri Huchard, 75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9727-1592","authenticated-orcid":false,"given":"Pauline","family":"Arnaud","sequence":"additional","affiliation":[{"name":"Laboratory for Vascular Translational Science, INSERM U1148, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri Huchard, 75018 Paris, France"},{"name":"D\u00e9partement de G\u00e9n\u00e9tique, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri 17 Huchard, 75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Hanna","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri 17 Huchard, 75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Jondeau","sequence":"additional","affiliation":[{"name":"Laboratory for Vascular Translational Science, INSERM U1148, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri Huchard, 75018 Paris, France"},{"name":"Centre de R\u00e9f\u00e9rence pour le Syndrome de Marfan et syndromes apparent\u00e9s, Service de Cardiologie, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri Huchard, 75018 Paris, France"},{"name":"UFR de M\u00e9decine, Universit\u00e9 Paris Diderot, 16 rue Henri Huchard, 75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0371-7539","authenticated-orcid":false,"given":"Catherine","family":"Boileau","sequence":"additional","affiliation":[{"name":"Laboratory for Vascular Translational Science, INSERM U1148, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri Huchard, 75018 Paris, France"},{"name":"D\u00e9partement de G\u00e9n\u00e9tique, Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri 17 Huchard, 75018 Paris, France"},{"name":"UFR de M\u00e9decine, Universit\u00e9 Paris Diderot, 16 rue Henri Huchard, 75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/nar\/25.1.147","article-title":"Marfan Database (second edition): software and database for the analysis of mutations in the human FBN1 gene","volume":"25","author":"Black","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1136\/jmg.2009.072785","article-title":"The revised Ghent nosology for the Marfan syndrome","volume":"47","author":"Loeys","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/gim.2014.91","article-title":"Increased frequency of FBN1 truncating and splicing variants in Marfan syndrome patients with aortic events","volume":"17","author":"Baudhuin","year":"2015","journal-title":"Genet. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13023-017-0754-6","article-title":"The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome","volume":"13","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1086\/520125","article-title":"Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: An international study","volume":"81","author":"Faivre","year":"2007","journal-title":"Am. J. Hum. 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