{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T18:23:51Z","timestamp":1790447031491,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T00:00:00Z","timestamp":1478476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>Classical Ehlers\u2013Danlos syndrome (cEDS) is a rare connective tissue disorder primarily characterized by hyperextensible skin, defective wound healing, abnormal scars, easy bruising, and generalized joint hypermobility; arterial dissections are rarely observed. Mutations in <jats:italic>COL5A1<\/jats:italic> and <jats:italic>COL5A2<\/jats:italic> encoding type V collagen account for more than 90% of the patients so far characterized. In addition, cEDS phenotype was reported in a small number of patients carrying the c.934C&gt;T mutation in <jats:italic>COL1A1<\/jats:italic> that results in an uncommon substitution of a non\u2010glycine residue in one Gly\u2010Xaa\u2010Yaa repeat of the pro\u2010\u03b11(I)\u2010chain p.(Arg312Cys), which leads to disturbed collagen fibrillogenesis due to delayed removal of the type I procollagen N\u2010propeptide. This specific mutation has been associated with propensity to arterial rupture in early adulthood; indeed, in literature the individuals harboring this mutation are also referred to as \u201c(classic) vascular\u2010like\u201d EDS patients. Herein, we describe a three\u2010generation cEDS family with six adults carrying the p.(Arg312Cys) substitution, which show a variable and prevalent cutaneous involvement without any major vascular event. These data, together with those available in literature, suggest that vascular events are not a diagnostic handle to differentiate patients with the p.(Arg312Cys) <jats:italic>COL1A1<\/jats:italic> mutation from those with <jats:italic>COL5A1<\/jats:italic> and <jats:italic>COL5A2<\/jats:italic> defects, and highlight that during the diagnostic process the presence of at least the p.(Arg312Cys) substitution in <jats:italic>COL1A1<\/jats:italic> should be investigated in cEDS patients without type V collagen mutations. Nevertheless, for these patients, as well as for those affected with cEDS, a periodical vascular surveillance should be carried out together with cardiovascular risk factors monitoring. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38035","type":"journal-article","created":{"date-parts":[[2016,11,7]],"date-time":"2016-11-07T10:57:36Z","timestamp":1478516256000},"page":"524-530","source":"Crossref","is-referenced-by-count":38,"title":["Delineation of Ehlers\u2013Danlos syndrome phenotype due to the c.934C&gt;T, p.(Arg312Cys) mutation in <i>COL1A1<\/i>: Report on a three\u2010generation family without cardiovascular events, and literature review"],"prefix":"10.1002","volume":"173","author":[{"given":"Marina","family":"Colombi","sequence":"first","affiliation":[{"name":"Department of Molecular and Translational Medicine, School of Medicine, Division of Biology and Genetics University of Brescia Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Dordoni","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, School of Medicine, Division of Biology and Genetics University of Brescia Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Venturini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Division of Dermatology Spedali Civili University Hospital Berscia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Zanca","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Division of Dermatology Spedali Civili University Hospital Berscia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiacomo","family":"Calzavara\u2010Pinton","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Division of Dermatology Spedali Civili University Hospital Berscia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Ritelli","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, School of Medicine, Division of Biology and Genetics University of Brescia Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,11,7]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2010.11.023"},{"key":"e_1_2_5_3_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O","article-title":"Ehlers\u2010Danlos syndromes: Revised nosology, villefranche","volume":"77","author":"Beighton P","year":"1998","journal-title":"Am J Med Genet A"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37365"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33541"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19971003)72:1<94::AID-AJMG20>3.0.CO;2-O"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20456"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31429"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34420"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2014.10.036"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22760"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000335123"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2007.00926.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.038224"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20455"},{"key":"e_1_2_5_16_1","volume-title":"GeneReviews\u2122 [internet]. 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