{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:51:07Z","timestamp":1786978267600,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T00:00:00Z","timestamp":1579737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570802"],"award-info":[{"award-number":["81570802"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873668"],"award-info":[{"award-number":["81873668"]}],"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;amp; Gen Med"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spondyloepiphyseal dysplasia congenita (SEDC) is an extremely rare inherited chondrodysplasia characterized by abnormal epiphyses, short stature, and flattened vertebral bodies. We investigate the phenotypes and the disease\u2010associated variants of SEDC in two unrelated Chinese families.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified disease\u2010associated variants in two nonconsanguineous families with SEDC using targeted next\u2010generation sequencing and confirmed the variants using Sanger sequencing. We investigated the phenotypes of the patients, including clinical manifestations, bone turnover biomarkers, bone mineral density and skeletal radiographic features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two probands were diagnosed as SEDC according to the phenotypes of disproportionately short\u2010trunk stature, kyphosis, lumbar lordosis and adduction deformity of hips. Radiographs revealed kyphosis and lumbar lordosis, flattened vertebral bodies, compressed femoral heads and shortening of the femurs. Bone mineral density of the probands\u00a0was lower than\u00a0that of age\u2010 and gender\u2010matched normal\u00a0children, but bone turnover biomarker levels were within normal range. Two novel heterozygous missense variants (NM_001844.5: c.1654 G&gt;A, NP_001835.3: p.Gly552Arg; NM_001844.5: c.3518G&gt;T, NP_001835.3: p.Gly1173Val) in collagen type II alpha 1 chain (\n                      <jats:italic>COL2A1<\/jats:italic>\n                      ) were detected in the two families, which would impair the formation of stable triple\u2010helical type II collagen.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We identified two novel disease\u2010associated variants in\n                      <jats:italic>COL2A1<\/jats:italic>\n                      , which led to severe SEDC. Our findings expanded the gene variant spectrum and phenotypic spectrum of extremely rare type II collagenopathies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.1139","type":"journal-article","created":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T19:10:34Z","timestamp":1579806634000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel variants in\n                    <i>COL2A1<\/i>\n                    causing rare spondyloepiphyseal dysplasia congenita"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1587-5067","authenticated-orcid":false,"given":"Wen\u2010bin","family":"Zheng","sequence":"first","affiliation":[{"name":"Key Laboratory of Endocrinology Department of Endocrinology National Health and Family Planning Commission Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u2010jiao","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology Department of Endocrinology National Health and Family Planning Commission Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di\u2010chen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology Department of Endocrinology National Health and Family Planning Commission Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ou","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology Department of Endocrinology National Health and Family Planning Commission Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology Department of Endocrinology National Health and Family Planning Commission Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010bo","family":"Xia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology Department of Endocrinology National Health and Family Planning Commission Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010ping","family":"Xing","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology Department of Endocrinology National Health and Family Planning Commission Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4380-3511","authenticated-orcid":false,"given":"Mei","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Endocrinology Department of Endocrinology National Health and Family Planning Commission Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,23]]},"reference":[{"issue":"5","key":"e_1_2_9_2_1","first-page":"896","article-title":"Spondyloepiphyseal dysplasia congenita: Genetic linkage to type II collagen (COL2AI)","volume":"46","author":"Anderson I. 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