{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:43:29Z","timestamp":1790361809898,"version":"4.1.0"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T00:00:00Z","timestamp":1617840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Classical Ehlers\u2010Danlos syndrome (cEDS) is a heterogeneous connective tissue disorder that mainly results from the germline mutation of <jats:italic>COL5A1<\/jats:italic> and <jats:italic>COL5A2<\/jats:italic>. The majority of the <jats:italic>COL5A2<\/jats:italic> mutations reported to date represent structural mutations, including missense or in\u2010frame exon\u2010skipping splice mutations. The only reported synonymous mutation was expected to affect on splicing of exon 29 by prediction programs which should be further confirmed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole exome sequencing was performed to identify the genetic variants of a Chinese boy who was characterized by skin hyperextensibility, abnormal scarring, hypermobile joints and scoliosis. Sanger sequencing was used to validate the variants in his parents. Reverse transcription polymerase chain reaction (RT\u2010PCR) was performed to analyze the functional effects of the variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A de novo heterozygous synonymous variant (NM_000393.5:c.1977 G&gt;A) of <jats:italic>COL5A2<\/jats:italic> gene was identified in the patient. The results of RT\u2010PCR revealed that the synonymous variant led to skipping of exon 29 in the RNA transcript.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study supplies further supporting evidence that the synonymous <jats:italic>COL5A2<\/jats:italic> mutation c.1977 G&gt;A can cause skipping of exon 29 in the RNA transcript, thus resulting in the production of mutant \u03b12(V)\u2010chains and clinical phenotype of cEDS. This result highlights the need to include splicing\u2010altering synonymous mutations into the screening for cEDS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1632","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T06:01:04Z","timestamp":1617948064000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Clinical and genetic analysis of classical Ehlers\u2010Danlos syndrome patient caused by synonymous mutation in <i>COL5A2<\/i>"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0089-7789","authenticated-orcid":false,"given":"Na","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital Changsha PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Changsha Central Hospital Changsha PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital Changsha PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0602-6063","authenticated-orcid":false,"given":"Ying","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital Changsha PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Reproductive and Genetic Hospital of CITIC\u2010Xiangya Changsha PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiling","family":"Tang","sequence":"additional","affiliation":[{"name":"Reproductive and Genetic Hospital of CITIC\u2010Xiangya Changsha PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengjun","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital Changsha PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9321-8479","authenticated-orcid":false,"given":"Hui","family":"Xi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital Changsha PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodi","family":"Gao","sequence":"additional","affiliation":[{"name":"Reproductive and Genetic Hospital of CITIC\u2010Xiangya Changsha PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Hunan Provincial Maternal and Child Health Care Hospital Changsha PR China"},{"name":"National Health Commission Key Laboratory of Birth Defects Research Prevention and Treatment Changsha PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5701-6703","authenticated-orcid":false,"given":"Juan","family":"Du","sequence":"additional","affiliation":[{"name":"Reproductive and Genetic Hospital of CITIC\u2010Xiangya Changsha PR China"},{"name":"Institute of Reproductive and Stem Cell Engineering School of Basic Medical Science Central South University Changsha PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-4328(00)00043-3"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.13.6049-6057.2004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13052"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3970"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.23330"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20107"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31552"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181eed412"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.2.249"},{"key":"e_1_2_9_11_1","first-page":"220","article-title":"Oral and mandibular manifestations in the Ehlers\u2010Danlos syndromes","volume":"175","author":"Mitakides J.","year":"2017","journal-title":"American Journal of Medical Genetics"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2015.11.022"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-58"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3051"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22137"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/342099"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1165"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1632","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1632","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1632","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T16:59:17Z","timestamp":1693414757000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,8]]},"references-count":16,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1002\/mgg3.1632"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1632","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,8]]},"assertion":[{"value":"2020-05-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1632"}}