{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:50:29Z","timestamp":1787316629148,"version":"build-2736575974"},"reference-count":15,"publisher":"Walter de Gruyter GmbH","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,26]]},"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n \n Achondroplasia and hypochondroplasia are the most common forms of disproportionate short stature, of which the vast majority of cases can be attributed to the hotspot missense mutations in the gene\n FGFR3<\/jats:italic>\n . Here we presented cases with a novel cryptic splicing variant of\n FGFR3<\/jats:italic>\n gene and aimed to interrogate the variant pathogenicity.\n <\/jats:p>\n <\/jats:sec>\n \n Case presentaiton<\/jats:title>\n \n In whole exome sequencing of two patients with hypochondroplasia-like features, a\n de novo<\/jats:italic>\n intronic variant c.1075\u00a0+\u00a095C>G was identified, predicted to alter mRNA splicing. Minigene assay showed that this intronic variant caused retention of a 90-nucleotide segment of intron 8 in mRNA, resulting in a 30-amino acid insertion at the extracellular domain of the protein. This is the first likely pathogenic splicing variant identified in the\n FGFR3<\/jats:italic>\n gene and was detected in one additional patient among 26 genetically unresolved patients.\n <\/jats:p>\n <\/jats:sec>\n \n Conclustions<\/jats:title>\n \n Our results strongly suggest that c.1075\u00a0+\u00a095C>G is a recurrent mutation and should be included in genetic testing of\n FGFR3<\/jats:italic>\n especially for those patients with equivocal clinical findings and no exonic mutations identified.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1515\/jpem-2020-0679","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T20:09:52Z","timestamp":1624478992000},"page":"1323-1328","source":"Crossref","is-referenced-by-count":3,"title":["An intronic variant disrupts mRNA splicing and causes\n FGFR3<\/i>\n -related skeletal dysplasia"],"prefix":"10.1515","volume":"34","author":[{"given":"Ting","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetics , Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research , Shanghai , China"},{"name":"Clinical Genetics Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetics , Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research , Shanghai , China"},{"name":"Clinical Genetics Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqian","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetics , Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research , Shanghai , China"},{"name":"Clinical Genetics Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetics , Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-0910","authenticated-orcid":false,"given":"Yongguo","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetics , Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research , Shanghai , China"},{"name":"Clinical Genetics Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research , Shanghai , China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition , 200092 , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Genetics , Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research , Shanghai , China"},{"name":"Clinical Genetics Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Institute for Pediatric Research , Shanghai , China"},{"name":"Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition , 200092 , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"2023040101125222591_j_jpem-2020-0679_ref_001","doi-asserted-by":"crossref","unstructured":"Pauli, RM. Achondroplasia: a comprehensive clinical review. Orphanet J Rare Dis 2019;14:1. https:\/\/doi.org\/10.1186\/s13023-018-0972-6.","DOI":"10.1186\/s13023-018-0972-6"},{"key":"2023040101125222591_j_jpem-2020-0679_ref_002","unstructured":"Legare, JM. Achondroplasia. In: Adam, MP, Ardinger, HH, Pagon, RA, et al.., editors. GeneReviews\u00ae [Internet] [Updated 2020 Aug 6]. Seattle (WA): University of Washington, Seattle; 1998:1993\u20132021 pp. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1152\/."},{"key":"2023040101125222591_j_jpem-2020-0679_ref_003","unstructured":"Bober, MB, Bellus, GA, Nikkel, SM, Tiller, GE. Hypochondroplasia. In: Adam, MP, Ardinger, HH, Pagon, RA, Wallace, SE, Bean, LJH, Stephens, K, Amemiya, A, editors. GeneReviews\u00ae [Internet] [updated 2020 May 7]. 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Genet Med 2015;17:405\u201324. https:\/\/doi.org\/10.1038\/gim.2015.30.","DOI":"10.1038\/gim.2015.30"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2020-0679\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2020-0679\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T14:58:24Z","timestamp":1680361104000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2020-0679\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,24]]},"references-count":15,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,7,20]]},"published-print":{"date-parts":[[2021,10,26]]}},"alternative-id":["10.1515\/jpem-2020-0679"],"URL":"https:\/\/doi.org\/10.1515\/jpem-2020-0679","relation":{},"ISSN":["0334-018X","2191-0251"],"issn-type":[{"value":"0334-018X","type":"print"},{"value":"2191-0251","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,24]]}}}