{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:03:59Z","timestamp":1791234239714,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,11,8]],"date-time":"2005-11-08T00:00:00Z","timestamp":1131408000000},"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 C"],"published-print":{"date-parts":[[2005,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Classic<\/jats:italic> Ehlers\u2013Danlos syndrome is a heritable disorder of connective tissue that is characterized by skin hyperextensibility, fragile and soft skin, delayed wound healing with formation of atrophic scars, easy bruising, and generalized joint hypermobility. Mutations in the <jats:italic>COL5A1<\/jats:italic> and the <jats:italic>COL5A2<\/jats:italic> gene, encoding the \u03b11 and the \u03b12\u2010chain of type V collagen respectively, are identified in approximately 50% of patients with a clinical diagnosis of <jats:italic>classic<\/jats:italic> EDS. In approximately one third of patients, the disease is caused by a mutation leading to a non\u2010functional <jats:italic>COL5A1<\/jats:italic> allele, and resulting in haplo\u2010insufficiency of type V collagen. In a smaller proportion of patients, a structural mutation in <jats:italic>COL5A1<\/jats:italic> or <jats:italic>COL5A2<\/jats:italic>, resulting in the production of a functionally defective type V collagen protein, is responsible for the phenotype. Inter\u2010 and intrafamilial phenotypic variability is observed, but no genotype\u2013phenotype correlations can be made so far. The relatively low mutation detection rate in the <jats:italic>COL5A1\/A2<\/jats:italic> genes suggests genetic heterogeneity. Indeed rarely mutations in type I collagen have been identified in patients with <jats:italic>classic<\/jats:italic> EDS. Mutations in the gene for tenascin\u2010X have been implicated in an autosomal recessive condition phenotypically overlapping with <jats:italic>classic<\/jats:italic> EDS. Several other candidate genes, such as decorin, have emerged from the study of transgenic mouse models with clinical and ultrastructural features reminiscent of <jats:italic>classic<\/jats:italic> EDS. However, to date, no human examples have been reported for these mouse models. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.c.30070","type":"journal-article","created":{"date-parts":[[2005,11,16]],"date-time":"2005-11-16T18:54:44Z","timestamp":1132167284000},"page":"17-23","source":"Crossref","is-referenced-by-count":85,"title":["Molecular genetics in <i>classic<\/i> Ehlers\u2013Danlos syndrome"],"prefix":"10.1002","volume":"139C","author":[{"given":"Fransiska","family":"Malfait","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"de Paepe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,11,8]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0195-31"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980428)77:1<31::AID-AJMG8>3.0.CO;2-O"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-4328(00)00043-3"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011742200"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12348978"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.1997.tb01055.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/301948"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.141.5.1277"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.3.729"},{"issue":"3","key":"e_1_2_5_11_1","first-page":"547","article-title":"Mutations in the COL5A1 gene are causal in the Ehlers\u2013Danlos syndromes I and II","volume":"60","author":"De Paepe A","year":"1997","journal-title":"Am J Hum Genet"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.10.1893"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.21.10325"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(20000103)90:1<72::AID-AJMG13>3.0.CO;2-C"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10373"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(95)80021-D"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004399900092"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.9.1649"},{"key":"e_1_2_5_19_1","article-title":"The molecular basis of classic Ehlers\u2013Danlos syndrome. 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