{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:04:46Z","timestamp":1791234286221,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T00:00:00Z","timestamp":1427932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Netherlands Heart Foundation","award":["2009T001"],"award-info":[{"award-number":["2009T001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Different forms of Ehlers\u2010Danlos syndrome (EDS) exist, with specific phenotypes and associated genes. Vascular EDS, caused by heterozygous mutations in the <jats:italic>COL3A1<\/jats:italic> gene, is characterized by fragile vasculature with a high risk of catastrophic vascular events at a young age. Classic EDS, caused by heterozygous mutations in the <jats:italic>COL5A1<\/jats:italic> or <jats:italic>COL5A2<\/jats:italic> genes, is characterized by fragile, hyperextensible skin and joint laxity. To date, vessel rupture in four unrelated classic EDS patients with a confirmed <jats:italic>COL5A1<\/jats:italic> mutation has been reported. We describe familial occurrence of a phenotype resembling vascular EDS in a mother and her two sons, who all died at an early age from arterial ruptures. Diagnostic Sanger sequencing in the proband failed to detect aberrations in <jats:italic>COL3A1<\/jats:italic>, <jats:italic>COL1A1, COL1A2, TGFBR1, TGFBR2, SMAD3<\/jats:italic>, and <jats:italic>ACTA2<\/jats:italic>. Next, the proband's DNA was analyzed using a next\u2010generation sequencing approach targeting 554 genes linked to vascular disease (VASCULOME project). A novel heterozygous mutation in <jats:italic>COL5A1<\/jats:italic> was detected, resulting in an essential glycine substitution at the C\u2010terminal end of the triple helix domain (NM_000093.4:c.4610G&gt;T; p.Gly1537Val). This mutation was also present in DNA isolated from autopsy material of the index's brother. No material was available from the mother, but the mutation was excluded in her parents, siblings and in the father of her sons, suggesting that the <jats:italic>COL5A1<\/jats:italic> mutation occurred in the mother's genome <jats:italic>de novo<\/jats:italic>. In conclusion, we report familial occurrence of lethal arterial events caused by a COL5A1 mutation. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36997","type":"journal-article","created":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T22:26:00Z","timestamp":1428013560000},"page":"1196-1203","source":"Crossref","is-referenced-by-count":55,"title":["Familial Ehlers\u2010Danlos syndrome with lethal arterial events caused by a mutation in <i>COL5A1<\/i>"],"prefix":"10.1002","volume":"167","author":[{"given":"Glen R","family":"Monroe","sequence":"first","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht (UMCU) Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Harakalova","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht (UMCU) Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia N","family":"van der Crabben","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht (UMCU) Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"Majoor\u2010Krakauer","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida M","family":"Bertoli\u2010Avella","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans L","family":"Moll","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery University Medical Center Utrecht (UMCU) Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn I","family":"Oranen","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Bethesda Hospital Hoogeveen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Dooijes","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht (UMCU) Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryan","family":"Vink","sequence":"additional","affiliation":[{"name":"Department of Pathology University Medical Center Utrecht (UMCU) Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nine V","family":"Knoers","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht (UMCU) Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Maugeri","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Pals","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics VU University Medical Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac J","family":"Nijman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht (UMCU) Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gijs","family":"van Haaften","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht (UMCU) Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette F","family":"Baas","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics University Medical Center Utrecht (UMCU) Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33541"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34420"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2012.01858.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"24727","DOI":"10.1016\/S0021-9258(18)54290-3","article-title":"The Pro\u2010\u03b11(V) Collagen Chain. Complete primary structure, distribution of expression, and comparison with the Pro\u2010\u03b11(X1) collagen chain","volume":"266","author":"Greenspan DS","year":"1991","journal-title":"J Biol Chem"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-5214(97)70349-5"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2011.396"},{"key":"e_1_2_6_8_1","first-page":"764659","article-title":"Ehlers Danlos Syndrome: An Unusual Presentation You Need to Know about","volume":"2013","author":"Karaa A","year":"2013","journal-title":"Case Rep Pediatr"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20455"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181eed412"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20429"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0032-1325118"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60960-9"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003093421001"},{"key":"e_1_2_6_15_1","volume-title":"Ehlers\u2010Danlos Syndrome Type IV","author":"Pepin MG","year":"1999"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a117596"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-006-0294-1"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66459-8"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22137"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1995.9961"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511528200"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.36997","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.36997","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.36997","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T01:47:23Z","timestamp":1696643243000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.36997"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,2]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1002\/ajmg.a.36997"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.36997","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,2]]}}}