{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:56:54Z","timestamp":1790575014727,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":269,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Osteogenesis imperfecta (OI) is a heterogeneous group of genetic skeletal disorders characterized by bone fragility and low bone mass, manifesting as multiple fractures and deformities of the spine and extremities. Although genotype\u2010phenotype correlations have been studied in various populations, large\u2010scale data in Koreans have been lacking. This study is aimed at characterizing the clinical and genetic spectrum of nonlethal OI in the Korean population and explore genotype\u2013phenotype associations. This retrospective cohort study analyzed 198 genetically confirmed Korean OI probands evaluated at a single center between 2004 and 2024, with clinical features reviewed and genetic testing performed using Sanger sequencing and targeted next\u2010generation sequencing. A total of 160 distinct pathogenic variants were identified, including 44 novel variants. Variant pathogenicity was assessed according to the ACMG\/AMP variant classification guidelines. Pathogenic variants of\n                    <jats:italic>COL1A1<\/jats:italic>\n                    and\n                    <jats:italic>COL1A2<\/jats:italic>\n                    accounted for 87.4% of cases, with\n                    <jats:italic>COL1A1<\/jats:italic>\n                    variants being the most prevalent (66.7%). Only 4.0% of cases had autosomal recessive OI. Glycine substitution (GS) variants were associated with significantly more severe phenotypes than other variants, including shorter height (median z\u2010score\u22123.67 [IQR \u22128.37 to \u22121.78] vs. \u22121.17 [\u22121.96 to \u22120.16],\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001) and earlier fracture onset (1.00 [0.00\u20138.25] vs. 15.00 [7.00\u201324.75] months,\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001). In\n                    <jats:italic>COL1A1<\/jats:italic>\n                    , GS variants closer to the C\u2010terminus correlated with significantly more severe height reduction (Spearman\n                    <jats:italic>\u03c1<\/jats:italic>\n                    = \u22120.478,\n                    <jats:italic>p<\/jats:italic>\n                    = 0.005). The genotype\u2013phenotype analysis confirmed the phenotypic severity of GS, particularly for variants closer to the C\u2010terminus of\n                    <jats:italic>COL1A1<\/jats:italic>\n                    , consistent with previous studies. Additionally, the identification of 44 novel variants expands the variant spectrum of OI. These findings provide valuable insights into genetic diagnosis, prognostic assessment, and clinical management of OI.\n                  <\/jats:p>","DOI":"10.1155\/humu\/5521427","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:38:20Z","timestamp":1790573900000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genotype and Phenotype of 198 Korean Patients With Nonlethal Osteogenesis Imperfecta: A Retrospective Cohort Study"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8501-4126","authenticated-orcid":false,"given":"Junpyo","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6312-9890","authenticated-orcid":false,"given":"Hye Ran","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0407-7828","authenticated-orcid":false,"given":"Jung Min","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4154-7964","authenticated-orcid":false,"given":"Chang Ho","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8519-2061","authenticated-orcid":false,"given":"Wonik","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-1455","authenticated-orcid":false,"given":"Mi Hyun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8514-377X","authenticated-orcid":false,"given":"Tae-Joon","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.4055\/cios20060"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36545"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab017"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00959-x"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2017.02.004"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00728-X"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241210004"},{"key":"e_1_2_9_8_2","volume-title":"Chapter 11 - Structural Consequences of Glycine Missense Mutations in Osteogenesis Imperfecta","author":"Brodsky B.","year":"2014"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.242"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.81"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-019-05076-6"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-017-4143-8"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23718"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2021.116293"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.331"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.3345\/kjp.2018.61.5.135"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm4.10174"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11832-010-0289-z"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD005088.pub4"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00361366"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.02.018"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9423"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.129"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.004"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-022-00871-4"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20410"},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13353-018-0444-7"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.816078"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-016-0083-1"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1149982"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1254695"},{"key":"e_1_2_9_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21438"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00979"},{"key":"e_1_2_9_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1675"},{"key":"e_1_2_9_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-023-02123-2"},{"key":"e_1_2_9_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-016-3709-1"},{"key":"e_1_2_9_38_2","volume-title":"Civil Act, Act No. 471 (Feb. 22, 1958), amended by Act No. 7427 (Mar. 31, 2005), art. 809 (Republic of Korea)","author":"Korea Legislation Research Institute","year":"2026"},{"key":"e_1_2_9_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-019-0373-x"},{"key":"e_1_2_9_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20429"},{"key":"e_1_2_9_41_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2880131"},{"key":"e_1_2_9_42_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1098\/rstb.2000.0760","article-title":"Folding Defects in Fibrillar Collagens","volume":"356","author":"Byers P. H.","year":"2001","journal-title":"Philosophical Transactions of the Royal Society of London. Series B"},{"key":"e_1_2_9_43_2","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/540178"},{"key":"e_1_2_9_44_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345231154569"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/5521427","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/humu\/5521427","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/5521427","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:38:23Z","timestamp":1790573903000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/humu\/5521427"}},"subtitle":[],"editor":[{"given":"Boon-Peng","family":"Hoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/humu\/5521427"],"URL":"https:\/\/doi.org\/10.1155\/humu\/5521427","archive":["Portico"],"relation":{},"ISSN":["1059-7794","1098-1004"],"issn-type":[{"value":"1059-7794","type":"print"},{"value":"1098-1004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-11-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"5521427"}}