{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:00:38Z","timestamp":1777622438597,"version":"3.51.4"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"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:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Osteogenesis imperfecta (OI) is a group of connective tissue disorders with significantly clinical and genetic heterogeneity, which is characterized by low bone mineral density, recurrent fractures and skeletal deformities. This study aimed to conduct clinical and genetic analyses in a Chinese OI cohort to expand the spectrum of pathogenic variants and provide evidence for precise genetic counseling and prenatal genetic diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 77 Chinese families with clinically suspected OI were enrolled in this study. Clinical assessments at enrollment included physical examinations, X-ray imaging, and bone mineral density testing. Whole exome sequencing (WES) combined with Sanger sequencing was used to detect candidate pathogenic variants. Variant pathogenicity was evaluated via bioinformatics analysis and familial co-segregation analysis. In this OI cohort, the spectra of pathogenic variants, clinical phenotypes, and genotype-phenotype correlations were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A 100% detection rate for pathogenic variants was achieved in the 77 families, with 79 variants identified in total. Among the 79 variants, 21 (26.6%) were novel variants founded across six OI-associated genes. Interestingly, apart from the correlation between different pathogenic genes and clinical phenotypes, we also discovered that the severity and phenotype of patients associated with the location of pathogenic variants within the type I collagen domain, exhibiting an aggravating trend from the amino terminus to the carboxyl terminus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Based on previous studies of large OI cohorts, we expanded the spectrum of pathogenic variants by identifying 21 novel ones. Meanwhile, we discovered that the location of pathogenic variants, particularly missense variants, in type I procollagen is correlated with the clinical manifestations and severity of patients. These findings will provide important evidence for the precise diagnosis and genetic counseling of the disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1825533","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T22:13:05Z","timestamp":1777414385000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["21 novel pathogenic variants identified in a cohort of 77 Chinese families with osteogenesis imperfecta"],"prefix":"10.3389","volume":"17","author":[{"given":"Binshan","family":"Zhao","sequence":"first","affiliation":[{"name":"Center for Rare Diseases, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaoqun","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, State Key Laboratory for Complex, Severe, and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siji","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences","place":["Beijing, China"]},{"name":"Department of Medical Genetics, State Key Laboratory for Complex, Severe, and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyuan","family":"Tao","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuzhi","family":"Ren","sequence":"additional","affiliation":[{"name":"Key Laboratory in Science and Technology Development Project of Suzhou (CN), Pediatric Orthopedics, Children\u2019s Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaping","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuli","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Rare Diseases, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences","place":["Beijing, China"]},{"name":"Department of Medical Genetics, State Key Laboratory for Complex, Severe, and Rare Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College","place":["Beijing, China"]},{"name":"Key Laboratory in Science and Technology Development Project of Suzhou (CN), Pediatric Orthopedics, Children\u2019s Hospital of Soochow University","place":["Suzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3607","DOI":"10.1007\/s00198-016-3709-1","article-title":"DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum","volume":"27","author":"Bardai","year":"2016","journal-title":"Osteoporos. 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