{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:55:02Z","timestamp":1780070102858,"version":"3.54.0"},"reference-count":35,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cDepartment of Rare Skeletal Disorders\u201d\u2014IRCCS Istituto Ortopedico Rizzoli for open access articlecessing charge (APC)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary osteoporosis in children and young adults often suggests a monogenic disease affecting bone microarchitecture and bone mineral density. While Osteogenesis Imperfecta (OI) is the most recognized genetic cause of recurrent fractures, many other genes involved in bone metabolism may contribute to osteoporosis. Among them, FGFR2 plays a critical role in bone growth and development by regulating osteoblast differentiation and proliferation, as well as chondrogenesis. Germline pathogenic FGFR2 variants are typically associated with syndromic craniosynostosis, conditions not characterized by bone fragility or osteoporosis. A report recently identified FGFR2 as a potential cause of dominant early-onset osteoporosis and bone fractures in a family. We report the case of a child affected by severe osteoporosis with multiple fractures. We performed clinical exome sequencing in trio to investigate potential genetic causes of the observed phenotype and identified a likely mosaic pathogenic FGFR2 variant, absent in both parental samples. Our findings provide further evidence that FGFR2 pathogenic variants can lead to a novel non-syndromic bone mineralization disorder, reinforcing the role of FGFR2 in the pathogenesis of early-onset osteoporosis.<\/jats:p>","DOI":"10.3390\/ijms26094204","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T07:49:36Z","timestamp":1745912976000},"page":"4204","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Further Evidence of Early-Onset Osteoporosis and Bone Fractures as a New FGFR2-Related Phenotype"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-341X","authenticated-orcid":false,"given":"Alice","family":"Moroni","sequence":"first","affiliation":[{"name":"Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9980-7741","authenticated-orcid":false,"given":"Elena","family":"Pedrini","sequence":"additional","affiliation":[{"name":"Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morena","family":"Tremosini","sequence":"additional","affiliation":[{"name":"Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5691-0786","authenticated-orcid":false,"given":"Alessia","family":"Di Cecco","sequence":"additional","affiliation":[{"name":"Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-3866","authenticated-orcid":false,"given":"Dario","family":"Cocciadiferro","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-4297","authenticated-orcid":false,"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Division of Pediatrics, Azienda Ospedaliero Universitaria delle Marche, Presidio Salesi, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Cordiali","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Division of Pediatrics, Azienda Ospedaliero Universitaria delle Marche, Presidio Salesi, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Sangiorgi","sequence":"additional","affiliation":[{"name":"Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5907-7470","authenticated-orcid":false,"given":"Maria","family":"Gnoli","sequence":"additional","affiliation":[{"name":"Department of Rare Skeletal Disorders, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0140-6736(18)32112-3","article-title":"Osteoporosis","volume":"393","author":"Compston","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1007\/s00198-022-06454-3","article-title":"Global, Regional Prevalence, and Risk Factors of Osteoporosis According to the World Health Organization Diagnostic Criteria: A Systematic Review and Meta-Analysis","volume":"33","author":"Xiao","year":"2022","journal-title":"Osteoporos. 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