{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:58:58Z","timestamp":1771930738033,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Osteogenesis imperfecta (OI) is a hereditary disorder primarily caused by mutations in\n                      <jats:italic>COL1A1<\/jats:italic>\n                      or\n                      <jats:italic>COL1A2<\/jats:italic>\n                      , leading to bone fragility and deformities. Although numerous pathogenic variants have been identified, novel mutations in specific populations remain underreported, complicating diagnosis and genetic counseling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A Chinese family with mild type I OI was recruited. Whole-exome sequencing and Sanger sequencing were used to identify and validate a novel splice-site variant in\n                      <jats:italic>COL1A1<\/jats:italic>\n                      . Functional effects were assessed using two minigene constructs (pcMINI-\n                      <jats:italic>COL1A1<\/jats:italic>\n                      and pcMINI-N-\n                      <jats:italic>COL1A1<\/jats:italic>\n                      ) transfected into HEK293T cells, followed by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing of transcripts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A novel heterozygous splice-site variant (c.298 + 1G&amp;gt;A) at the donor site of\n                      <jats:italic>COL1A1<\/jats:italic>\n                      intron 2 was identified and found to co-segregate with the disease. Minigene assays demonstrated that this mutation induces abnormal splicing patterns, including partial and complete skipping of exon 2, resulting in frameshifted transcripts with premature termination codons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The c.298 + 1G&amp;gt;A variant leads to aberrant splicing and likely haploinsufficiency, consistent with a mild OI phenotype. This study expands the\n                      <jats:italic>COL1A1<\/jats:italic>\n                      mutation spectrum and supports the use of functional assays for clarifying pathogenicity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1758799","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T22:10:08Z","timestamp":1770329408000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and functional characterization of a novel pathogenic COL1A1 splicing variant in a Chinese family with osteogenesis imperfecta"],"prefix":"10.3389","volume":"17","author":[{"given":"Hongjuan","family":"Nie","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People\u2019s Hospital","place":["Guigang, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanxiong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People\u2019s Hospital","place":["Guigang, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peifang","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People\u2019s Hospital","place":["Guigang, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guiming","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People\u2019s Hospital","place":["Guigang, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[{"name":"Precision Diagnosis Center, Xiangya Third Hospital of Central South University","place":["Changsha, Hunan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People\u2019s Hospital","place":["Guigang, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongjun","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Hand and Foot Reconstructive Microsurgery, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City People\u2019s Hospital","place":["Guigang, Guangxi, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"117572","DOI":"10.1016\/j.bone.2025.117572","article-title":"A real-world analysis of the clinical and healthcare burden associated with osteogenesis imperfecta","volume":"200","author":"Abraham","year":"2025","journal-title":"Bone"},{"key":"B2","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s13353-018-0444-7","article-title":"Splicing mutations in human genetic disorders: examples, detection, and confirmation","volume":"59","author":"Anna","year":"2018","journal-title":"J. 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