{"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":1788873716800,"version":"build-2803163510"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"15","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation Project of China","doi-asserted-by":"crossref","award":["32060165"],"award-info":[{"award-number":["32060165"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Haploinsufficiency resulting from the degradation of mutant Collagen Type X Alpha 1 Chain (COL10A1) mRNA by nonsense-mediated decay (NMD) has been attributed to the pathogenesis of Schmid-type metaphyseal chondrodysplasia (SMCD) in cases involving nonsense mutations. However, this mechanism does not fully explain the complexity of SMCD. In this study, we identified a c.1951_1952 InsT (p.W651 fsX666) mutation in exon 3 of COL10A1 that is associated with chondrodysplasia phenotypes in a two-generation family with SMCD. The mRNA decay of the mutant COL10A1 (named as affected E666X-COL10A1) is caused by the p.W651fsX666 mutation, which also disrupts the trimerization of normal collagen X. However, the mutant mRNA decay of affected exogenous E666X-COL10A1, as well as the complete degradation of E666X-COL10A1 mRNA in the proband, is not significantly induced by the W651fsX666 mutation. In vitro trimerization analyses results indicate that the trimerization of normal collagen X and wild-type collagen X are disrupted by W651fsX666 and E666X-collagen X mutations, respectively, suggesting that the mutant allele collagen X may impose a dominant-negative effect on the normal collagen X. Our results are the first to reveal that the impaired trimerization of normal collagen X is caused by the W651fsX666 mutation and a dominant-negative effect on the normal allele collagen X exerted by the mutant allele collagen X, causing impaired trimerization of collagen X, which will interpret the phenotype variability among the affected individuals in the pedigree with metaphyseal chondrodysplasia type Schmid (MCDS) studied.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf071","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T18:54:22Z","timestamp":1747853662000},"page":"1265-1285","source":"Crossref","is-referenced-by-count":5,"title":["The p.W651fsX666 mutation on <i>COL10A1<\/i> results in impaired trimerization of normal collagen X to induce Schmid type Metaphyseal chondrodysplasia"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9060-0372","authenticated-orcid":false,"given":"Jingye","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, the Affiliated Hospital of Guizhou Medical University , #16 Beijing Road, Guiyang, Guizhou 550004 ,","place":["P.R. 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Medicine, Guizhou Provincial People\u2019s Hospital \uff0c #83 East Zhongshan Road, Guiyang\uff0c Guiyang, Guizhou 550001 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Laboratory, Yongchuan People\u2019s Hospital of Chongqing , #375 Huilong Avenue, Yongchuan District, Chongqing 402160 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology, the Affiliated Hospital of Guizhou Medical University , #16 Beijing Road, Guiyang, Guizhou 550004 ,","place":["P. R. 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Vascular and Thyroid Surgery, Guizhou Provincial People\u2019s Hospital , #83 East Zhongshan Road, Guiyang 550002 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxia","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, the Affiliated Hospital of Guizhou Medical University , #16 Beijing Road, Guiyang, Guizhou 550004 ,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxue","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, the Affiliated Hospital of Guizhou Medical University , #16 Beijing Road, Guiyang, Guizhou 550004 ,","place":["P.R. 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