{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:51:59Z","timestamp":1766065919014,"version":"3.48.0"},"reference-count":17,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"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 (OI) type XIV is a rare recessive disorder caused by TMEM38B pathogenic variants that disrupt an endoplasmic reticulum protein essential for calcium homeostasis and bone mineralization. This leads to severe bone fragility, early-onset fractures, skeletal deformities, low bone mass, scoliosis, and variable features like blue sclerae or dental abnormalities. We present a case report of a 21-year-old Italian male with a novel homozygous TMEM38B splice variant (c.112 + 1G &gt; T), detailing the clinical presentation, genetic findings, and therapeutic outcomes. The patient exhibited multiple skeletal deformities and showed a moderate response to bisphosphonate therapy (neridronate). In addition, a systematic review of PubMed and Scopus identified 12 relevant studies from an initial set of 82 publications, encompassing data from 56 patients diagnosed with OI type XIV. Unlike classical collagen-related OI, TMEM38B-related OI necessitates genetic screening beyond classical collagen genes (COL1A1 and COL1A2). While bisphosphonates provide some clinical benefit, persistent fractures underscore the need for long-term management and innovative therapies. This case report and systematic review enhance understanding of OI type XIV and underscore the clinical importance of TMEM38B variants in bone fragility disorders.<\/jats:p>","DOI":"10.3390\/ijms262412169","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T13:45:07Z","timestamp":1766065507000},"page":"12169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Previously Unreported TMEM38B Variant in Osteogenesis Imperfecta Type XIV: A Case Report and Systematic Review of the Literature"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5429-6036","authenticated-orcid":false,"given":"Thomas","family":"Zoller","sequence":"first","affiliation":[{"name":"Pediatric Unit, Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Verona University Medical School, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Righetti","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Verona University Medical School, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Cont","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Verona University Medical School, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5378-1895","authenticated-orcid":false,"given":"Ruggero","family":"Lanzafame","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Verona University Medical School, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Ambrosetti","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Verona University Medical School, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Guzzo","sequence":"additional","affiliation":[{"name":"Department of Pathology and Diagnostics, School of Medicine, Verona University Medical School, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9912-3232","authenticated-orcid":false,"given":"Angelo","family":"Pietrobelli","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Verona University Medical School, 37134 Verona, Italy"},{"name":"Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1405-1792","authenticated-orcid":false,"given":"Franco","family":"Antoniazzi","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Surgical Science, Dentistry, Gynecology and Pediatrics, Verona University Medical School, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17052","DOI":"10.1038\/nrdp.2017.52","article-title":"Osteogenesis imperfecta","volume":"3","author":"Marini","year":"2017","journal-title":"Nat. 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