{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T21:46:24Z","timestamp":1771969584372,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31700731"],"award-info":[{"award-number":["31700731"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Osteogenesis imperfecta (OI), a rare autosomal inheritable disorder characterized by bone fragility and skeletal deformity, is caused by pathogenic variants in genes impairing the synthesis and processing of extracellular matrix protein collagen type I. With the use of next\u2010generation sequencing and panels approaches, an increasing number of OI patients can be confirmed and new pathogenic variants can be discovered. This study sought to identify pathogenic gene variants in a Chinese family with OI I.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010exome sequencing was used to identify pathogenic variants in the proband, which is confirmed by Sanger sequencing and cosegregation analysis; MES, HSF, and Spliceman were used to analyze this splicing variant\uff1bqRT\u2010PCR was performed to identify the mRNA expression level of <jats:italic>COL1A1<\/jats:italic> in patient peripheral blood samples; Minigene splicing assay was performed to mimic the splicing process of <jats:italic>COL1A1<\/jats:italic> variants in vitro; Analysis of evolutionary conservation of amino acid residues and structure prediction of the mutant protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel splicing pathogenic variant (c.3814+1G&gt;T) was identified in this OI family by using whole\u2010exome sequencing, Sanger sequencing, and cosegregation analysis. Sequencing of RT\u2010PCR products from the <jats:italic>COL1A1<\/jats:italic> minigene variant reveals a 132\u2010nucleotide (nt) insertion exists at the junction between exons 48 and exon 49 of the <jats:italic>COL1A1<\/jats:italic> cDNA. Splicing assay indicates that the mutated minigene produces an alternatively spliced transcript which may cause a frameshift resulting in early termination of protein expression. The molecular analysis suggested that the altered amino acid is located at the C\u2010terminus of type I procollagen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study reveals the pathogenesis of a novel <jats:italic>COL1A1<\/jats:italic> splicing pathogenic variant c.3814+1G&gt;T in a Chinese family with OI I.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1366","type":"journal-article","created":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T06:00:30Z","timestamp":1593151230000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A novel splicing pathogenic variant in <i>COL1A1<\/i> causing osteogenesis imperfecta (OI) type I in a Chinese family"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6340-6225","authenticated-orcid":false,"given":"Yaxin","family":"Han","sequence":"first","affiliation":[{"name":"The Graduate School Shanxi Medical University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongming","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Hospital Shanxi Medical University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinli","family":"Guo","sequence":"additional","affiliation":[{"name":"The Second Hospital Shanxi Medical University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1531-7353","authenticated-orcid":false,"given":"Qiuhong","family":"Xiong","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6137-6154","authenticated-orcid":false,"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5015-7688","authenticated-orcid":false,"given":"Yong\u2010An","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Second Hospital Shanxi Medical University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Second Hospital Shanxi Medical University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn374"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076\u20106879(82)82062\u20104"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.2000.3039"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(15)00728\u2010X"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)35449-3"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00979"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00060"},{"key":"e_1_2_9_9_1","first-page":"360","article-title":"A novel COL1A1 nonsense mutation causing osteogenesis imperfecta in a Chinese family","volume":"13","author":"Liu W.","year":"2007","journal-title":"Molecular Vision"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.5582\/irdr.2019.01064"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37547"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.28.120194.000245"},{"issue":"5","key":"e_1_2_9_13_1","first-page":"453","article-title":"When cells stop making sense: effects of nonsense codons on RNA metabolism in vertebrate cells","volume":"1","author":"Maquat L. 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