{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:28:20Z","timestamp":1791725300529,"version":"4.3.4"},"reference-count":27,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteogenesis imperfecta type VI is a rare autosomal recessive disorder characterized by bone fragility and defective mineralization, caused by pathogenic variants in the SERPINF1 gene. This study aimed to expand the understanding of OI type VI by analyzing clinical, radiological, and molecular findings in four patients from three unrelated families. Genotyping revealed two novel SERPINF1 variants, c.185G&gt;T (p.Gly62Val) and c.992_993insCA (p.Glu331Asnfs), in a compound heterozygous state in one patient, and a known pathogenic variant, c.261_265dup (p.Leu89Argfs26), in a homozygous form in three patients. Clinical manifestations included early-onset fractures, severe skeletal deformities, impaired mobility, and growth failure. Radiological assessments revealed multilevel and multiplanar bone deformities and metaphyseal widening. RNA analysis demonstrated that the c.992_993insCA variant results in a truncated PEDF protein without triggering nonsense-mediated decay. Population screening identified a carrier frequency of 0.0044 for the c.261_265dup variant, suggesting a founder effect in the Tuvinian population. These findings expand the mutational spectrum of the SERPINF1 gene and provide new insights into the phenotypic variability of OI type VI. Our results highlight the importance of genetic screening in isolated populations and emphasize the need for further research to develop more effective therapeutic approaches for patients with limited response to bisphosphonate therapy.<\/jats:p>","DOI":"10.3390\/ijms26136200","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T05:28:28Z","timestamp":1751347708000},"page":"6200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Molecular and Clinical Aspects of Osteogenesis Imperfecta Type VI: A Case Series with Novel SERPINF1 Gene Variants"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6902-253X","authenticated-orcid":false,"given":"Elena S.","family":"Merkuryeva","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4527-4518","authenticated-orcid":false,"given":"Tatyana S.","family":"Nagornova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7651-8485","authenticated-orcid":false,"given":"Vladimir M.","family":"Kenis","sequence":"additional","affiliation":[{"name":"The Turner Scientific Research Institute for Children\u2019s Orthopedics, 196603 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna S.","family":"Deviataikina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daria B.","family":"Akimova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1868-3703","authenticated-orcid":false,"given":"Dmitry S.","family":"Buklaev","sequence":"additional","affiliation":[{"name":"The Turner Scientific Research Institute for Children\u2019s Orthopedics, 196603 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4024-5171","authenticated-orcid":false,"given":"Ilya S.","family":"Dantsev","sequence":"additional","affiliation":[{"name":"Veltischev Research and Clinical Institute for Pediatrics, Pirogov Russian National Research Medical University, 125412 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisluu O.","family":"Dulush","sequence":"additional","affiliation":[{"name":"Perinatal Center of the Republic of Tyva, 667000 Kyzyl, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina Y.","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2672-6294","authenticated-orcid":false,"given":"Tatiana V.","family":"Markova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17052","DOI":"10.1038\/nrdp.2017.52","article-title":"Osteogenesis imperfecta","volume":"3","author":"Krakow","year":"2017","journal-title":"Nat. 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