{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:00:23Z","timestamp":1768453223093,"version":"3.49.0"},"reference-count":14,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970698"],"award-info":[{"award-number":["31970698"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The protein encoded by the cartilage oligomeric matrix protein (<jats:italic>COMP<\/jats:italic>) gene is a noncollagenous extracellular matrix (ECM) protein that is important for chondrocyte formation and growth. Variations in the <jats:italic>COMP<\/jats:italic> gene cause pseudoachondroplasia (PSACH), which is mainly characterized by short\u2010limbed dwarfing in the clinic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To characterize the function of a rare pathogenic variant in the <jats:italic>COMP<\/jats:italic> gene (c.875G\u00a0&gt;\u00a0A, p.Cys292Tyr).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials &amp; Methods<\/jats:title><jats:p>We performed 3D structural analysis, in vitro expression analysis, and immunofluorescence to characterize the effects of the variant on protein structure, expression, and cellular localization respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Variation modeling showed that the interactions between amino acids were changed after the variation, and there were 31 changes in the secondary structure of mutant COMP (MT\u2010COMP). Western blot showed that the intracellular quantity of MT\u2010COMP was higher than the wild\u2010type COMP (WT\u2010COMP). Cellular immunofluorescence results showed that WT\u2010COMP was less abundant and homogenously distributed in cells, while the MT\u2010COMP accumulated in the cytoplasm.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Herein, we report a variant of <jats:italic>COMP<\/jats:italic> in a Chinese family with PSACH. We have shown that the rare missense variant, <jats:italic>COMP<\/jats:italic> c.875G\u00a0&gt;\u00a0A, previously reported in ClinVar and identified in our patient, results in excessive accumulation of mutant protein in the cytoplasm, and is therefore pathogenic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Through in silico and experimental analyses, we provide evidence that <jats:italic>COMP<\/jats:italic> c.875G\u00a0&gt;\u00a0A is the likely cause of PSACH in a Chinese family.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.12521","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T07:50:41Z","timestamp":1689666641000},"page":"241-247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional characterization of a rare pathogenic variant c.875G\u00a0&gt;\u00a0A, p.(Cys292Tyr) in <i>COMP<\/i>"],"prefix":"10.1111","volume":"87","author":[{"given":"Lan","family":"Yin","sequence":"first","affiliation":[{"name":"Department of Medical Genetics West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingchuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenhao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yilu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dachang","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongxin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics West China Hospital, Sichuan University Chengdu Sichuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0795\u2010330"},{"key":"e_1_2_9_3_1","volume-title":"GeneReviews\u00ae","author":"Briggs M. 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