{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:32:26Z","timestamp":1777462346234,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T00:00:00Z","timestamp":1638144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["202102020100"],"award-info":[{"award-number":["202102020100"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2020A1515110545"],"award-info":[{"award-number":["2020A1515110545"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82102636"],"award-info":[{"award-number":["82102636"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vascular Ehlers\u2010Danlos syndrome (vEDS) is a rare and severe hereditary connective tissue disease arising from a mutation in the type III collagen alpha I chain (<jats:italic>COL3A1<\/jats:italic>) gene, with a poor prognosis due to exceptional vascular ruptures and premature death. Herein, starting from a 36\u2010year\u2010old Chinese male patient with a complaint of upper abdominal pain, we collected clinical data of and performed a genetic analysis of a total of 20 family members. We identified two closely spaced <jats:italic>COL3A1<\/jats:italic>\u00a0missense variants in <jats:italic>cis<\/jats:italic>, p.Leu734Phe (c.2199_2200TC&gt;AT) and p.Gly741Ser (c.2221G&gt;A), as the cause of vEDS in this family. p.Gly741Ser, a glycine substitution mutation, has been previously reported, whereas p.Leu734Phe, a non\u2010glycine substitution mutation, is novel. We analysed their independent and combined effects on the COL3A1\u00a0level in transfected skin fibroblast cells by means of Western blotting. We found that both variants independently led to a reduced COL3A1\u00a0level and, when combined, led to an even more reduced COL3A1\u00a0level compared to the wild type. Thus, each missense variant can be independently classified as a pathogenic variant, albeit with a synergetic effect when occurring together. Moreover, our genetic findings provide an explanation for four previous sudden deaths and identified two high\u2010risk carriers in the family.<\/jats:p>","DOI":"10.1111\/jcmm.17063","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T16:31:50Z","timestamp":1638289910000},"page":"144-150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Two closely spaced missense <i>COL3A1<\/i> variants in <i>cis<\/i> cause vascular Ehlers\u2010Danlos syndrome in one large Chinese family"],"prefix":"10.1111","volume":"26","author":[{"given":"Mei","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1824-6116","authenticated-orcid":false,"given":"Chong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Radiology First Affiliated Hospital Sun Yat\u2010Sen University Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunbing","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yushun","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31553"},{"key":"e_1_2_9_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_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.04.013"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003093421001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1538574417692114"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.32"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2014.181"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.72"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00284038"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130730"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0470-9"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23296"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12349"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1159\/000491956"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.113.000280"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31550"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2019.05.003"}],"container-title":["Journal 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