{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T20:36:44Z","timestamp":1773175004399,"version":"3.50.1"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Campomelic dysplasia (CD) is an autosomal dominant skeletal dysplasia syndrome characterized by shortness and bowing of lower extremities, and often accompanied by XY sex reversal. Heterozygous pathogenic variants of <jats:italic>SOX9<\/jats:italic> or rearrangement involving the long arm of chromosome 17 are the causes of disease. However, evidence for pathogenesis of <jats:italic>SOX9<\/jats:italic> haploinsufficiency is insufficient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled a Chinese family where the fetus was diagnosed with CD. The affected fetus was selected for whole-exome sequencing to identify the pathogenic mutations in this family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After data filtering, a novel non-sense <jats:italic>SOX9<\/jats:italic> variant (NM_000346.3; c.1249C\u2009&amp;gt;\u2009T; p.Q417*) was identified as the pathogenic lesion in the fetus. Further co-segregation analysis using Sanger sequencing confirmed that this novel <jats:italic>SOX9<\/jats:italic> mutation (c.1249C\u2009&amp;gt;\u2009T; p.Q417*) was a <jats:italic>de novo<\/jats:italic> mutation in the affected fetus. This terminated codon mutation identified by bioinformatics was located at an evolutionarily conserved site of <jats:italic>SOX9<\/jats:italic>. The bioinformatics-based analysis predicted this variant was pathogenic and affected <jats:italic>SOX9<\/jats:italic> transactivation activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>CD is a rare condition, which connected with <jats:italic>SOX9<\/jats:italic> tightly. We identified a novel heterozygous <jats:italic>SOX9<\/jats:italic> variant (p.Q417*) in a Chinese CD family. Our study supports the putative reduced transactivation of <jats:italic>SOX9<\/jats:italic> variants in the pathogenicity of CD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2022.1089194","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T07:49:27Z","timestamp":1674028167000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case report: A de novo Non-sense SOX9 mutation (p.Q417*) located in transactivation domain is Responsible for Campomelic Dysplasia"],"prefix":"10.3389","volume":"10","author":[{"given":"Xingxing","family":"Qiao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianjun","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangliang","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaqin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1046\/j.1469-0705.2000.00126.x","article-title":"Prenatal 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