{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T03:33:45Z","timestamp":1785900825774,"version":"3.56.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"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. Genet."],"abstract":"<jats:p>Spondyloepiphyseal dysplasia congenital (SEDC) is a rare chondrodysplasia caused by dominant pathogenic variants in <jats:italic>COL2A1<\/jats:italic>. Here, we detected a novel variant c.3392G &amp;gt; T (NM_001844.4) of <jats:italic>COL2A1<\/jats:italic> in a Chinese family with SEDC by targeted next-generation sequencing. To confirm the pathogenicity of the variant, we generated an appropriate minigene construct based on HeLa and HEK293T cell lines. Splicing assay indicated that the mutated minigene led to aberrant splicing of <jats:italic>COL2A1<\/jats:italic> pre-mRNA and produced an alternatively spliced transcript with a skipping of partial exon 48, which generated a predicted in-frame deletion of 15 amino acids (p. Gly1131_Pro1145del) in the COL2A1 protein. Due to the pathogenicity of the variation, we performed prenatal diagnosis on the proband\u2019s wife, which indicated that the fetus carried the same mutation.<\/jats:p>","DOI":"10.3389\/fgene.2022.827560","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T13:13:58Z","timestamp":1649164438000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["A Novel Mutation c.3392G&gt;T of COL2A1 Causes Spondyloepiphyseal Dysplasia Congenital by Affecting Pre-mRNA Splicing"],"prefix":"10.3389","volume":"13","author":[{"given":"Lihong","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longfei","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosong","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefeng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisi","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,5]]},"reference":[{"key":"B1","first-page":"896","article-title":"Spondyloepiphyseal Dysplasia Congenita: Genetic Linkage to Type II Collagen (COL2AI)","volume":"46","author":"Anderson","year":"1990","journal-title":"Am. J. Hum. Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1042\/cs20160211","article-title":"RNA Splicing in Human Disease and in the Clinic","volume":"131","author":"Baralle","year":"2017","journal-title":"Clin. Sci. (Lond)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.3390\/genes12091395","article-title":"A Novel Splicing Variant of COL2A1 in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions","volume":"12","author":"Bruni","year":"2021","journal-title":"Genes"},{"key":"B4","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1002\/pd.1525","article-title":"Sonographic Diagnosis of SEDC and Double Heterozygote of SEDC and Achondroplasia-A Report of Six Pregnancies","volume":"26","author":"Chitty","year":"2006","journal-title":"Prenat. Diagn."},{"key":"B5","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1002\/ajmg.a.61049","article-title":"Exome Sequencing Reveals a Novel COL2A1 Mutation Implicated in Multiple Epiphyseal Dysplasia","volume":"179","author":"Dasa","year":"2019","journal-title":"Am. J. Med. Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mrrev.2016.02.003","article-title":"Molecular Genetics of the COL2A1-Related Disorders","volume":"768","author":"Deng","year":"2016","journal-title":"Mutat. Research\/Reviews Mutat. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.1002\/ajmg.a.35301","article-title":"Spondyloperipheral Dysplasia as the Mosaic Form of Platyspondylic Lethal Skeletal Dyplasia torrance Type in Mother and Fetus with the sameCOL2A1mutation","author":"D\u00e9sir","year":"2012","journal-title":"Am. J. Med. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2815","DOI":"10.1002\/ajmg.a.32047","article-title":"A Familial Case of Achondrogenesis Type II Caused by a dominantCOL2A1 Mutation and \"patchy\" Expression in the Mosaic Father","author":"Forzano","year":"2007","journal-title":"Am. J. Med. Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1016\/j.addr.2003.08.002","article-title":"Collagens-structure, Function, and Biosynthesis","volume":"55","author":"Gelse","year":"2003","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1007\/s10157-020-01876-x","article-title":"Functional Analysis of Suspected Splicing Variants in CLCN5 Gene in Dent Disease 1","volume":"24","author":"Inoue","year":"2020","journal-title":"Clin. Exp. Nephrol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"173","DOI":"10.7863\/jum.1990.9.3.173","article-title":"Antenatal Sonographic Appearance of Spondyloepiphyseal Dysplasia Congenita","volume":"9","author":"Kirk","year":"1990","journal-title":"J. Ultrasound Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"a006143","DOI":"10.1101\/mcs.a006143","article-title":"Genome Sequencing Identifies Three Molecular Diagnoses Including a Mosaic Variant in the COL2A1 Gene in an Individual with Pol III-Related Leukodystrophy and Feingold Syndrome","volume":"7","author":"Muirhead","year":"2021","journal-title":"Cold Spring Harb Mol. Case Stud."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1002\/ajmg.a.35303","article-title":"Somatic Mosaicism and the Phenotypic Expression of COL2A1 Mutations","author":"Nagendran","year":"2012","journal-title":"Am. J. Med. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1002\/humu.20179","article-title":"The Phenotypic Spectrum ofCOL2A1mutations","volume":"26","author":"Nishimura","year":"2005","journal-title":"Hum. Mutat."},{"key":"B14","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1148\/radiology.196.2.7617874","article-title":"Homozygous Achondroplasia: US Distinction between Homozygous, Heterozygous, and Unaffected Fetuses in the Second Trimester","volume":"196","author":"Patel","year":"1995","journal-title":"Radiology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"5154","DOI":"10.3390\/ijms22105154","article-title":"Principles and Practical Considerations for the Analysis of Disease-Associated Alternative Splicing Events Using the Gateway Cloning-Based Minigene Vectors pDESTsplice and pSpliceExpress","volume":"22","author":"Putscher","year":"2021","journal-title":"Ijms"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e1005756","DOI":"10.1371\/journal.pgen.1005756","article-title":"Exonic Splicing Mutations Are More Prevalent Than Currently Estimated and Can Be Predicted by Using In Silico Tools","volume":"12","author":"Soukarieh","year":"2016","journal-title":"Plos Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/bf02011911","article-title":"Kniest Dysplasia Is Caused by Dominant Collagen II (COL2A1) Mutations: Parental Somatic Mosaicism Manifesting as Stickler Phenotype and Mild Spondyloepiphyseal Dysplasia","volume":"24","author":"Spranger","year":"1994","journal-title":"Pediatr. Radiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/gm13","article-title":"The Human Gene Mutation Database: 2008 Update","volume":"1","author":"Stenson","year":"2009","journal-title":"Genome Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"585064","DOI":"10.3389\/fgene.2020.585064","article-title":"Six Exonic Variants in the SLC5A2 Gene Cause Exon Skipping in a Minigene Assay","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/ng0493-323","article-title":"Kniest and Stickler Dysplasia Phenotypes Caused by Collagen Type II Gene (COL2A1) Defect","volume":"3","author":"Winterpacht","year":"1993","journal-title":"Nat. Genet."},{"key":"B21","doi-asserted-by":"publisher","first-page":"17059","DOI":"10.1038\/hgv.2017.59","article-title":"A Novel De Novo Mutation in COL2A1 Leading to Spondyloepiphyseal Dysplasia Congenita in a Chinese Family","volume":"5","author":"Xiong","year":"2018","journal-title":"Hum. Genome"},{"key":"B22","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1002\/ajmg.a.61422","article-title":"Parental Somatogonadal COL2A1 Mosaicism Contributes to Intrafamilial Recurrence in a Family with Type 2 Collagenopathy","volume":"182","author":"Yamamoto","year":"2020","journal-title":"Am. J. Med. Genet."},{"key":"B23","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1111\/cge.13680","article-title":"Integrated Analysis ofCOL2A1variant Data and Classification of Type II Collagenopathies","volume":"97","author":"Zhang","year":"2020","journal-title":"Clin. Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e1139","DOI":"10.1002\/mgg3.1139","article-title":"Novel Variants in COL2A1 Causing Rare Spondyloepiphyseal Dysplasia Congenita","volume":"8","author":"Zheng","year":"2020","journal-title":"Mol. Genet. Genomic Med."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.827560\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T18:54:31Z","timestamp":1656960871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.827560\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,5]]},"references-count":25,"alternative-id":["10.3389\/fgene.2022.827560"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.827560","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,5]]},"article-number":"827560"}}