{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:29:03Z","timestamp":1790774943946,"version":"4.1.0"},"reference-count":46,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2024,1,18]]},"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Marfan syndrome (MFS) is a multisystem disease with a unique combination of skeletal, cardiovascular and ocular features. Geleophysic\/acromicric dysplasias (GPHYSD\/ACMICD), characterised by short stature and extremities, are described as \u2018the mirror image\u2019 of MFS. The numerous <jats:italic>FBN1<\/jats:italic> pathogenic variants identified in MFS are located all along the gene and lead to the same final pathogenic sequence. Conversely, in GPHYSD\/ACMICD, the 28 known heterozygous <jats:italic>FBN1<\/jats:italic> pathogenic variants all affect exons 41\u201342 encoding TGF\u03b2-binding protein-like domain 5 (TB5).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Since 1996, more than 5000 consecutive probands have been referred nationwide to our laboratory for molecular diagnosis of suspected MFS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified five MFS probands carrying distinct heterozygous pathogenic in-frame variants affecting the TB5 domain of FBN1. The clinical data showed that the probands displayed a classical form of MFS. Strikingly, one missense variant affects an amino acid that was previously involved in GPHYSD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Surprisingly, pathogenic variants in the TB5 domain of FBN1 can lead to two opposite phenotypes: GPHYSD\/ACMICD and MFS, suggesting the existence of different pathogenic sequences with the involvement of tissue specificity. Further functional studies are ongoing to determine the precise role of this domain in the physiopathology of each disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg-2023-109646","type":"journal-article","created":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T13:20:46Z","timestamp":1709904046000},"page":"469-476","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Pathogenic variants affecting the TB5 domain of the fibrillin-1 protein: not only in geleophysic\/acromicric dysplasias but also in Marfan syndrome"],"prefix":"10.1136","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9727-1592","authenticated-orcid":false,"given":"Pauline","family":"Arnaud","sequence":"first","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique, Assistance Publique - Hopitaux de Paris, Paris, France"},{"name":"U1148 LVTS, INSERM, Paris, \u00cele-de-France, France"},{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares Syndrome de Marfan et apparent\u00e9s, H\u00f4pital Bichat, APHP, Paris, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-2865","authenticated-orcid":false,"given":"Zakaria","family":"Mougin","sequence":"additional","affiliation":[{"name":"U1148 LVTS, INSERM, Paris, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve","family":"Baujat","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique, AP-HP, H\u00f4pital Necker-Enfants malades, AP-HP, Paris, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Drouin-Garraud","sequence":"additional","affiliation":[{"name":"D\u00e9partement de P\u00e9diatrie, CHU de Rouen, Rouen, Normandie, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salima","family":"El Chehadeh","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, H\u00f4pital de Hautepierre, CHU de Strasbourg, Strasbourg, Grand Est, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Gouya","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares Syndrome de Marfan et apparent\u00e9s, H\u00f4pital Bichat, APHP, Paris, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Odent","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Clinique, CLAD Ouest, CHU Rennes, Rennes, Bretagne, France"},{"name":"UMR 6290, IGDR, Rennes, Bretagne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Jondeau","sequence":"additional","affiliation":[{"name":"U1148 LVTS, INSERM, Paris, \u00cele-de-France, France"},{"name":"Centre de R\u00e9f\u00e9rence Maladies Rares Syndrome de Marfan et apparent\u00e9s, H\u00f4pital Bichat, APHP, Paris, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Boileau","sequence":"additional","affiliation":[{"name":"D\u00e9partement de G\u00e9n\u00e9tique, Assistance Publique - 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