{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:16:19Z","timestamp":1791206179311,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82270496"],"award-info":[{"award-number":["82270496"]}]},{"name":"National Natural Science Foundation of China","award":["81830031"],"award-info":[{"award-number":["81830031"]}]},{"name":"National Natural Science Foundation of China","award":["81970969"],"award-info":[{"award-number":["81970969"]}]},{"name":"National Natural Science Foundation of China","award":["82001088"],"award-info":[{"award-number":["82001088"]}]},{"name":"National Natural Science Foundation of China","award":["82101054"],"award-info":[{"award-number":["82101054"]}]},{"name":"National Natural Science Foundation of China","award":["MBExC"],"award-info":[{"award-number":["MBExC"]}]},{"name":"German Research Foundation through the Multiscale Bioimaging Cluster of Excellence","award":["82270496"],"award-info":[{"award-number":["82270496"]}]},{"name":"German Research Foundation through the Multiscale Bioimaging Cluster of Excellence","award":["81830031"],"award-info":[{"award-number":["81830031"]}]},{"name":"German Research Foundation through the Multiscale Bioimaging Cluster of Excellence","award":["81970969"],"award-info":[{"award-number":["81970969"]}]},{"name":"German Research Foundation through the Multiscale Bioimaging Cluster of Excellence","award":["82001088"],"award-info":[{"award-number":["82001088"]}]},{"name":"German Research Foundation through the Multiscale Bioimaging Cluster of Excellence","award":["82101054"],"award-info":[{"award-number":["82101054"]}]},{"name":"German Research Foundation through the Multiscale Bioimaging Cluster of Excellence","award":["MBExC"],"award-info":[{"award-number":["MBExC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Skeletal Class III malocclusion with maxillary deficiency is a severe maxillofacial disease with unclear pathogenic mechanisms. We recruited a Han Chinese family who was clinically diagnosed with skeletal Class III malocclusion and maxillary deficiency. Using whole exome sequencing, a missense variant in ADAMTS2 (NM_014244: c.3506G&gt;T: p.G1169V) was identified and predicted as deleterious by in silico tools. We also found ADAMTS2 variants associated with deficient maxillary development in a cohort. ADAMTS2 expression in HEK293 cells showed significant decrease due to the variant, which was also consistent in dental pulp stem cells from the proband and a healthy control. In the adamts2-knockdown zebrafish model, the length and width of the ethmoid plate, as well as the length of the palatoquadrate became significantly shorter than the control group (p &lt; 0.001), while there was no significant difference in the length and width of the mandible. The expression of Sox3, which was required in early embryonic craniofacial development, was significantly downregulated in the adamts2-knockdown zebrafish embryos. Bioinformatic and cellular studies showed that the decreased expression of ADAMTS2 may inhibit downstream ErbB signaling pathway transduction and restrain subsequent osteogenesis in human adult mesenchymal stromal cells. Collectively, these data showed that ADAMTS2 (c.3506G&gt;T: p.G1169V) may confer susceptibility to risk of skeletal Class III malocclusion with maxillary deficiency.<\/jats:p>","DOI":"10.3390\/ijms231810673","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T20:50:45Z","timestamp":1663188645000},"page":"10673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Skeletal Class III Malocclusion Is Associated with ADAMTS2 Variants and Reduced Expression in a Familial Case"],"prefix":"10.3390","volume":"23","author":[{"given":"Siyue","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing 210000, China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210000, China"},{"name":"The Affiliated Stomatology Hospital of Suzhou Vocational Health College, Suzhou 215000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing 210000, China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-3447","authenticated-orcid":false,"given":"Barbara","family":"Vona","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center G\u00f6ttingen, 37073 G\u00f6ttingen, Germany"},{"name":"Institute for Auditory Neuroscience and Inner Ear Lab, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing 210000, China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing 210000, China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing 210000, China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yuan","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210000, China"},{"name":"Department of Oral and Maxillofacial Surgery, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Du","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210000, China"},{"name":"Department of Oral and Maxillofacial Surgery, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Ma","sequence":"additional","affiliation":[{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongchu","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Affiliated Stomatology Hospital of Nanjing Medical University, Nanjing 210000, China"},{"name":"Jiangsu Province Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing 210000, China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1007\/s00784-020-03731-5","article-title":"Genetic factors contributing to skeletal class III malocclusion: A systematic review and meta-analysis","volume":"25","year":"2021","journal-title":"Clin. 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