{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T18:29:34Z","timestamp":1777573774351,"version":"3.51.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T00:00:00Z","timestamp":1501804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Bone Material Laboratory of the Ludwig Boltzmann Institute of Osteology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Mutations in the PLS3 gene, encoding Plastin 3, were described in 2013 as a cause for X-linked primary bone fragility in children. The specific role of PLS3 in bone metabolism remains inadequately understood. Here we describe for the first time PLS3 deletions as the underlying cause for childhood-onset primary osteoporosis in 3 boys from 2 families. We carried out thorough clinical, radiological, and bone tissue analyses to explore the consequences of these deletions and to further elucidate the role of PLS3 in bone homeostasis. In family 1, the 2 affected brothers had a deletion of exons 4\u201316 (NM_005032) in PLS3, inherited from their healthy mother. In family 2, the index patient had a deletion involving the entire PLS3 gene (exons 1\u201316), inherited from his mother who had osteoporosis. The 3 patients presented in early childhood with severe spinal compression fractures involving all vertebral bodies. The 2 brothers in family 1 also displayed subtle dysmorphic facial features and both had developed a myopathic gait. Extensive analyses of a transiliac bone biopsy from 1 patient showed a prominent increase in osteoid volume, osteoid thickness, and in mineralizing lag time. Results from quantitative backscattered electron imaging and Raman microspectroscopy showed a significant hypomineralization of the bone. Together our results indicate that PLS3 deletions lead to severe childhood-onset osteoporosis resulting from defective bone matrix mineralization, suggesting a specific role for PLS3 in the mineralization process. \u00a9 2017 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3233","type":"journal-article","created":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T12:46:42Z","timestamp":1501850802000},"page":"2394-2404","source":"Crossref","is-referenced-by-count":48,"title":["<i>PLS3<\/i> Deletions Lead to Severe Spinal Osteoporosis and Disturbed Bone Matrix Mineralization"],"prefix":"10.1093","volume":"32","author":[{"given":"Anders J","family":"K\u00e4mpe","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Surgery and Center for Molecular MedicineKarolinska InstitutetStockholmSweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Costantini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery and Center for Molecular MedicineKarolinska InstitutetStockholmSweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yael","family":"Levy-shraga","sequence":"additional","affiliation":[{"name":"Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael"},{"name":"Pediatric Endocrinology UnitEdmond and Lily Safra Children's HospitalSheba Medical CenterTel-HashomerIsrael"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonid","family":"Zeitlin","sequence":"additional","affiliation":[{"name":"Pediatric Orthopedic DepartmentDana-Dwek Children's Hospital, Tel Aviv Sourasly Medical CenterTel AvivIsrael"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Roschger","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling1st Medical DepartmentHanusch HospitalViennaAustria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fulya","family":"Taylan","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery and Center for Molecular MedicineKarolinska InstitutetStockholmSweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Lindstrand","sequence":"additional","affiliation":[{"name":"Department of Clinical GeneticsKarolinska University HospitalStockholmSweden"},{"name":"Department of Molecular Medicine and Surgery and Center for Molecular MedicineKarolinska InstitutetStockholmSweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleftherios P","family":"Paschalis","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling1st Medical DepartmentHanusch HospitalViennaAustria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Gamsjaeger","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling1st Medical DepartmentHanusch HospitalViennaAustria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annick","family":"Raas-Rothschild","sequence":"additional","affiliation":[{"name":"Institute for Rare DiseasesThe Danek Gertner Institute of Human GeneticsSheba Medical CenterTel-HashomerIsrael"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"H\u00f6vel","sequence":"additional","affiliation":[{"name":"Department of Orthopedics and Trauma SurgeryUniversity Hospital Essen and the University of Duisburg-EssenEssenGermany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Nutritionand Science for Life LaboratoryKarolinska InstitutetStockholmSweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Klaushofer","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling1st Medical DepartmentHanusch HospitalViennaAustria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinna","family":"Grasemann","sequence":"additional","affiliation":[{"name":"Klinik f\u00fcr Kinderheilkunde IIUniversity Hospital Essen and the University of Duisburg-EssenEssenGermany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Outi","family":"M\u00e4kitie","sequence":"additional","affiliation":[{"name":"Folkh\u00e4lsan Institute of Genetics 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