{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:43:05Z","timestamp":1790026985415,"version":"4.0.1"},"reference-count":13,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"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":[[2019,5]]},"abstract":"<jats:p>Cardiac valvular Ehlers\u2010Danlos syndrome (EDS) is a rare EDS subtype, caused by specific recessive variants in the gene encoding pro\u2010\u03b12\u2010chain of type I collagen (<jats:italic>COL1A2<\/jats:italic>). Cardiac valvular EDS is mainly characterized by generalized\/peripheral joint hypermobility, moderate\u2013severe cardiac valvular disease, skin hyperextensibility and other minor soft tissues features. Only five molecularly confirmed patients have been reported to date. Here, we describe two additional affected sisters, who share the homozygous c.3601G&gt;T nonsense variant in <jats:italic>COL1A2<\/jats:italic>. Clinical data and literature review allowed to better define the clinical spectrum of cardiac valvular EDS which now emerges as a more recognizable EDS variant with progressive heart valve disease firstly affecting the mitral valve. Possibly distinguishing features include bilateral flatfeet with hindfoot pronation, lower eyelid ptosis and hypoplasia of the interphalangeal creases. The absence of bone fragility in our patients indicates that cardiac valvular EDS is also separated from patients with autosomal recessive osteogenesis imperfecta and variants in <jats:italic>COL1A2<\/jats:italic>, as well as from individuals with autosomal dominant osteogenesis imperfecta and severe cardiac valvular disease.<\/jats:p>","DOI":"10.1002\/ajmg.a.61100","type":"journal-article","created":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T08:48:34Z","timestamp":1551430114000},"page":"846-851","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Cardiac valvular Ehlers\u2010Danlos syndrome is a well\u2010defined condition due to recessive <i>null<\/i> variants in <i>COL1A2<\/i>"],"prefix":"10.1002","volume":"179","author":[{"given":"Vito","family":"Guarnieri","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Fondazione IRCCS\u2010Casa Sollievo della Sofferenza  San Giovanni Rotondo (FG) 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