{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T18:29:22Z","timestamp":1777573762594,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Osteogenesis imperfecta (OI) represents a complex spectrum of genetic bone diseases that occur primarily due to mutations and deletions of the COL1A1 and COL1A2 genes. Recent molecular studies of the network of signaling pathways have contributed to a better understanding of bone remodeling and the pathogenesis of OI caused by mutations in many other genes associated with normal bone mineralization. In this paper, a case of a rare X-linked variant of OI with a change in the gene encoding plastin 3\u2014a protein important for the regulation of the actin cytoskeleton, is presented. A 16-year-old patient developed ten bone fractures caused by minor trauma or injury, including a compression fracture of the second lumbar vertebra during his lifetime. Next-generation sequencing analysis did not show pathologically relevant deviations in the COL1A1 and COL1A2 genes. Targeted gene analyses (Skeletal disorder panel) of the patient, his father, mother and sister were then performed, detecting variants of uncertain significance (VUS) for genes PLS3, FN1 and COL11A2. A variant in the PLS3 gene were identified in the patient, his mother and sister. Since the PLS3 gene is located on the X chromosome, the mother and sister showed no signs of the disease. Although the variant in the PLS3 gene (c.685G&gt;A (p.Gly229Arg)) has not yet been described in the literature, nor is its pathogenicity known, clinical findings combined with genetic testing showed that this variant may explain the cause of X-linked OI in our patient. This rare case of the PLS3 variant of X-linked OI might point to a novel target for personalized therapy in patients with this severe disease.<\/jats:p>","DOI":"10.3390\/genes12121851","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T02:46:08Z","timestamp":1637721968000},"page":"1851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["X-Linked Osteogenesis Imperfecta Possibly Caused by a Novel Variant in PLS3"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8022-4095","authenticated-orcid":false,"given":"Petar","family":"Brlek","sequence":"first","affiliation":[{"name":"St. Catherine Specialty Hospital, 49210 Zabok\/10000 Zagreb, Croatia"},{"name":"Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6713-1273","authenticated-orcid":false,"given":"Darko","family":"Anti\u010devi\u0107","sequence":"additional","affiliation":[{"name":"St. Catherine Specialty Hospital, 49210 Zabok\/10000 Zagreb, Croatia"},{"name":"Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5361-6499","authenticated-orcid":false,"given":"Vilim","family":"Molnar","sequence":"additional","affiliation":[{"name":"St. Catherine Specialty Hospital, 49210 Zabok\/10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4536-285X","authenticated-orcid":false,"given":"Vid","family":"Mati\u0161i\u0107","sequence":"additional","affiliation":[{"name":"St. Catherine Specialty Hospital, 49210 Zabok\/10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Robinson","sequence":"additional","affiliation":[{"name":"Invitae, San Francisco, CA 94103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swaroop","family":"Aradhya","sequence":"additional","affiliation":[{"name":"Invitae, San Francisco, CA 94103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalibor","family":"Krpan","sequence":"additional","affiliation":[{"name":"Polyclinic \u201cK-Center\u201d, for Internal Medicine, Gynecology, Radiology, Physical Medicine and Rehabilitation, 10 000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dragan","family":"Primorac","sequence":"additional","affiliation":[{"name":"St. Catherine Specialty Hospital, 49210 Zabok\/10000 Zagreb, Croatia"},{"name":"Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Department of Biochemistry & Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA"},{"name":"The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, West Haven, CT 06516, USA"},{"name":"Medical School, University of Split, 21000 Split, Croatia"},{"name":"School of Medicine, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia"},{"name":"Medical School, University of Rijeka, 51000 Rijeka, Croatia"},{"name":"Medical School REGIOMED, 96 450 Coburg, Germany"},{"name":"Medical School, University of Mostar, 88000 Mostar, Bosnia and Herzegovina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jovanovic, M., Guterman-Ram, G., and Marini, J.C. (2021). Osteogenesis Imperfecta: Mechanisms and Signaling Pathways Connecting Classical and Rare OI Types. Endocr. 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