{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:05:25Z","timestamp":1784199925766,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Spondyloepi(meta)physeal dysplasias (SE[M]D) are a group of inherited skeletal disorders that mainly affect bone and cartilage, and next\u2010generation sequencing has aided the detection of genetic defects of such diseases. In this study, we aimed to identify causative variants in four Chinese families associated with SE(M)D.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited four unrelated Chinese families all displaying short stature and growth retardation. Clinical manifestations and X\u2010ray imaging were recorded for all patients. Candidate variants were identified by whole\u2010exome sequencing (WES) and verified by Sanger sequencing. Pathogenicity was assessed by conservation analysis, 3D protein modeling and in silico prediction, and was confirmed according to American College of Medical Genetics and Genomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three novel SE(M)D\u2010related variants c.1090dupG, c.7168\u00a0T\u00a0&gt;\u00a0G, and c.2947G\u00a0&gt;\u00a0C in <jats:italic>ACAN<\/jats:italic>, and one reported variant c.712C\u00a0&gt;\u00a0T in <jats:italic>PAPSS2<\/jats:italic> were identified. Among them, c.1090dupG in <jats:italic>ACAN<\/jats:italic> and c.712C\u00a0&gt;\u00a0T in <jats:italic>PAPSS2<\/jats:italic> caused truncated protein and the other two variants led to amino acid alterations. Conservation analysis revealed sites of the two missense variants were highly conserved, and bioinformatic findings confirmed their pathogenicity. 3D modeling of mutant protein encoded by c.7168\u00a0T\u00a0&gt;\u00a0G(p.Trp2390Gly) in <jats:italic>ACAN<\/jats:italic> proved the structural alteration in protein level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggested <jats:italic>ACAN<\/jats:italic> is a common pathogenic gene of SE(M)D. This study enriched the genetic background of skeletal dysplasias, and expanded the mutation spectra of <jats:italic>ACAN<\/jats:italic> and <jats:italic>PAPSS2<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1916","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T09:41:14Z","timestamp":1646818874000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of variants in <i>ACAN<\/i> and <i>PAPSS2<\/i> leading to spondyloepi(meta)physeal dysplasias in four Chinese families"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6025-637X","authenticated-orcid":false,"given":"Yixuan","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &amp; School of Basic Medicine Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &amp; School of Basic Medicine Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &amp; School of Basic Medicine Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9429-2889","authenticated-orcid":false,"given":"Nan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &amp; School of Basic Medicine Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &amp; School of Basic Medicine Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Peking Union Medical College Hospital Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8238-6311","authenticated-orcid":false,"given":"Xiuli","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences &amp; School of Basic Medicine Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980806)78:5<468::AID-AJMG13>3.0.CO;2-D"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155412464376"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.013342"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61282"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1517\/21678707.2015.1083853"},{"issue":"2","key":"e_1_2_10_7_1","first-page":"197","article-title":"District differences and regional division of heights among Chinese Han children and adolescents","volume":"33","author":"Cai C. 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