{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:21:56Z","timestamp":1788873716144,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"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>Schmid\u2010type metaphyseal chondrodysplasia (SMCD) is a rare autosomal dominant skeletal dysplasia caused by heterozygous mutations in <jats:italic>COL10A1<\/jats:italic>, the gene which encodes collagen type X alpha 1 chain. However, its genotype\u2013phenotype relationship has not been fully determined.<\/jats:p><jats:p>Subjects and Methods<\/jats:p><jats:p>The proband is a 2\u2010year\u2010old boy, born of non\u2010consanguineous Chinese parents. We conducted a systematic analysis of the clinical and radiological characteristics and a follow\u2010up study of the proband. Whole\u2010exome sequencing was applied for the genetic analysis, together with bioinformatic analysis of predicted consequences of the identified variant. A homotrimer model was built to visualize the affected region and predict possible outcomes of this variant. Furthermore, a literature review and genotype\u2013phenotype analysis were performed by online searching all cases with SMCD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel heterozygous variant (NM_000493.4: c.1863_1866delAATG, NP_000484.2: p.(Met622\u00a0Thrfs*54)) was identified in <jats:italic>COL10A1<\/jats:italic> gene in the affected child. And it was predicted to be pathogenic by <jats:italic>in silico<\/jats:italic> analysis. Protein modeling revealed that the variant was located in the NC1 domain, which was predicted to produce truncated collagen and impair the trimerization of collagen type X alpha 1 chain and combination with molecules in the matrix. Moreover, genotype\u2013phenotype correlation analysis demonstrated that patients with truncating variants or variants in NC1 domain often presented earlier onset and severer symptoms compared with those with non\u2010truncating or variants in non\u2010NC1 domains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The NC1 domain of <jats:italic>COL10A1<\/jats:italic> was proved to be the hotspot region underlying SMCD, patients with variants in NC1 domain were more likely to present severer manifestations at an earlier age.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1668","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T15:53:10Z","timestamp":1616687590000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Characterization of a novel <i>COL10A1<\/i> variant associated with Schmid\u2010type metaphyseal chondrodysplasia and a literature review"],"prefix":"10.1002","volume":"9","author":[{"given":"Huixiao","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Shandong Provincial Hospital Cheeloo College of Medicine Shandong University Jinan China"},{"name":"Department of Endocrinology and Metabolism Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"},{"name":"Institute of Endocrinology Shandong Academy of Clinical Medicine Jinan China"},{"name":"Shandong Clinical Medical Center of Endocrinology and Metabolism Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Shandong Provincial Hospital Cheeloo College of Medicine Shandong University Jinan China"},{"name":"Department of Endocrinology and Metabolism Dongying people's Hospital Dongying China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guimei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pediatric Orthopedics Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology Shandong Academy of Clinical Medicine Jinan China"},{"name":"Shandong Clinical Medical Center of Endocrinology and Metabolism Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Endocrinology Shandong Academy 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