{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:03:37Z","timestamp":1792641817533,"version":"4.5.0"},"reference-count":15,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T00:00:00Z","timestamp":1545091200000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:p>Recessive variants in <jats:italic>LTBP2<\/jats:italic> are associated with eye\u2010restricted phenotypes including (a) primary congenital glaucoma and (b) microspherophakia\/megalocornea and ectopia lentis with\/without secondary glaucoma. Nosology of <jats:italic>LTBP2<\/jats:italic> pathology in humans is apparently in contrast with the consolidated evidence of a wide expression of this gene in the developing embryo. Accordingly, in previously published patients with <jats:italic>LTBP2<\/jats:italic>\u2010related eye disease, additional extraocular findings have been occasionally reported and include, among others, high\u2010arched palate, tall stature, and variable cardiac involvement. Anyway, no emphasis was put on such systemic manifestations. Here, we report two unrelated Roma\/Gypsy patients first ascertained for a multisystem disorder mainly characterized by primary congenital glaucoma, complex congenital heart defect, tall stature, long fingers, skin striae and dystrophic scarring, and resembling Marfan syndrome. Heart involvement was severe with polyvalvular heart dysplasia in one, and transposition of great arteries, thoracic arterial tortuosity, polyvalvular heart dysplasia, and neo\u2010aortic root dilatation in the other. Both patients were homozygous for the recurrent c.895C&gt;T[p.(R299X)] variant, typically found in individuals of Roma\/Gypsy descent with an eye\u2010restricted phenotype. Our findings point out <jats:italic>LTBP2<\/jats:italic> as responsible of a systemic phenotype coherent with the community of syndromes related to anomalies in genes involved in the TGF\u03b2\u2010pathway. Among these disorders, <jats:italic>LTBP2<\/jats:italic>\u2010related systemic disease emerges as a distinct condition with expanding prognostic implications and autosomal recessive inheritance.<\/jats:p>","DOI":"10.1002\/ajmg.a.10","type":"journal-article","created":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T13:10:08Z","timestamp":1545138608000},"page":"104-112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>LTBP2<\/i>\u2010related \u201cMarfan\u2010like\u201d phenotype in two Roma\/Gypsy subjects with the <i>LTBP2<\/i> homozygous p.R299X variant"],"prefix":"10.1002","volume":"179","author":[{"given":"Silvia","family":"Morlino","sequence":"first","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Molecular Medicine Sapienza University, San Camillo\u2010Forlanini Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viola","family":"Alesi","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics IRCCS\u2010Bambino Ges\u00f9 Children Hospital and Research Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Cal\u00ec","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology and Arrhythmology Unit, Department of Pediatric Cardiology and Cardiac Surgery IRCCS\u2010Bambino Ges\u00f9 Children Hospital and Research Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5331-0473","authenticated-orcid":false,"given":"Francesca Romana","family":"Lepri","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics IRCCS\u2010Bambino Ges\u00f9 Children Hospital and Research Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelio","family":"Secinaro","sequence":"additional","affiliation":[{"name":"Division of Radiology IRCCS\u2010Bambino Ges\u00f9 Children Hospital and Research Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Grammatico","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Department of Molecular Medicine Sapienza University, San Camillo\u2010Forlanini Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics IRCCS\u2010Bambino Ges\u00f9 Children Hospital and Research Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Drago","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology and Arrhythmology Unit, Department of Pediatric Cardiology and Cardiac Surgery IRCCS\u2010Bambino Ges\u00f9 Children Hospital and Research Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6069-0993","authenticated-orcid":false,"given":"Marco","family":"Castori","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS Casa Sollievo della Sofferenza  San Giovanni Rotondo (Foggia) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9428-4934","authenticated-orcid":false,"given":"Anwar","family":"Baban","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology and Arrhythmology Unit, Department of Pediatric Cardiology and Cardiac Surgery IRCCS\u2010Bambino Ges\u00f9 Children Hospital and Research Institute  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.017"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.181"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2010.11"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43714"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.03.002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22105"},{"key":"e_1_2_7_8_1","first-page":"333","article-title":"Contribution of the latent transforming growth factor\u2010\u03b2 binding protein 2 gene to etiology of primary open angle glaucoma and pseudoexfoliation syndrome","volume":"19","author":"Jelodari\u2010Mamaghani S.","year":"2013","journal-title":"Molecular Vision"},{"key":"e_1_2_7_9_1","first-page":"2570","article-title":"Congenital megalocornea with zonular weakness and childhood lens\u2010related secondary glaucoma \u2013 A distinct phenotype caused by recessive LTBP2 mutations","volume":"17","author":"Khan A. 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