{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:28:12Z","timestamp":1789972092457,"version":"4.0.1"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2003,8,1]],"date-time":"2003-08-01T00:00:00Z","timestamp":1059696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Three different insertion mutations in the TNFRSF11A gene affecting the signal peptide of RANK have been described. An 18-bp duplication at position 84 (84dup18) is associated with the clinical syndrome of familial expansile osteolysis (FEO), whereas a 15-bp duplication at the same site (84dup15) causes the syndrome of expansile skeletal hyperphosphatasia (ESH). Here we report the phenotype of patients harboring a 27-bp duplication at position 75 (75dup27) in RANK. Affected individuals had hearing impairment and tooth loss beginning in the second or third decade. Radiographs of affected bones showed lytic and sclerotic lesions with bony enlargement and deformity. Serum alkaline phosphatase levels were elevated between 2 and 17 times above the normal range. Most patients had pelvic and skull involvement, and all had involvement of the mandible and maxilla. Most patients also had bony enlargement of the small joints of the hands, and one developed hypercalcemia during a period of immobilization. We conclude that the 75dup27 mutation of RANK causes a Paget's disease of bone-like phenotype that is distinct from, but which overlaps with, FEO and ESH. A particularly striking feature was involvement of the mandible and maxilla, but it remains to be seen if this is a specific feature of the 75dup27 mutation until further kindreds with this mutation are reported.<\/jats:p>","DOI":"10.1359\/jbmr.2003.18.8.1381","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T05:55:56Z","timestamp":1146117356000},"page":"1381-1385","source":"Crossref","is-referenced-by-count":110,"title":["Phenotypic Characterization of Early Onset Paget's Disease of Bone Caused by a 27-bp Duplication in the <i>TNFRSF11A<\/i> Gene"],"prefix":"10.1093","volume":"18","author":[{"given":"Kiyoshi","family":"Nakatsuka","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Metabolism and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart H","family":"Ralston","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Institute of Medical Sciences, Aberdeen University Medical School, Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019124387000_bib1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/71667","article-title":"Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis","volume":"24","author":"Hughes","year":"2000","journal-title":"Nat Genet"},{"key":"2024013019124387000_bib2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1097\/00005792-200203000-00002","article-title":"Familial expansile osteolysis (excessive RANK effect) in a 5-generation American kindred","volume":"81","author":"Whyte","year":"2002","journal-title":"Medicine (Baltimore)"},{"key":"2024013019124387000_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jmg.39.10.e67","article-title":"Familial expansile osteolysis in a large Spanish kindred resulting from an insertion mutation in the TNFRSF11A gene","volume":"39","author":"Palenzuela","year":"2002","journal-title":"J Med Genet"},{"key":"2024013019124387000_bib4","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1359\/jbmr.2000.15.12.2330","article-title":"Expansile skeletal hyperphosphatasia: A new familial metabolic bone disease","volume":"15","author":"Whyte","year":"2000","journal-title":"J Bone Miner Res"},{"key":"2024013019124387000_bib5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1359\/jbmr.2002.17.1.26","article-title":"Expansile skeletal hyperphosphatasia is caused by a 15-base pair tandem duplication in TNFRSF11A encoding RANK and is allelic to familial expansile osteolysis","volume":"17","author":"Whyte","year":"2002","journal-title":"J Bone Miner Res"},{"key":"2024013019124387000_bib6","first-page":"41","volume-title":"Pathophysiology and Treatment of Paget's Disease of Bone","author":"Kanis","year":"1992"},{"key":"2024013019124387000_bib7","first-page":"265","author":"Wallace","year":"1989"},{"key":"2024013019124387000_bib8","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1056\/NEJM198205133061903","article-title":"Calcium homeostasis in immobilization: An example of resorptive hypercalciuria","volume":"306","author":"Stewart","year":"1982","journal-title":"N Engl J Med"},{"key":"2024013019124387000_bib9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1056\/NEJMoa013096","article-title":"Osteoprotegerin deficiency and juvenile Paget's disease","volume":"347","author":"Whyte","year":"2002","journal-title":"N Engl J Med"},{"key":"2024013019124387000_bib10","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1093\/hmg\/11.18.2119","article-title":"A mutation in the gene TNFRSF11B encoding osteoprotegerin causes an idiopathic hyperphosphatasia phenotype","volume":"11","author":"Cundy","year":"2002","journal-title":"Hum Mol Genet"},{"key":"2024013019124387000_bib11","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1086\/340731","article-title":"Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1\/p62) in Paget disease of bone","volume":"70","author":"Laurin","year":"2002","journal-title":"Am J Hum Genet"},{"key":"2024013019124387000_bib12","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1093\/hmg\/11.22.2735","article-title":"Domain specific mutations in Sequestosome 1 (SQSTM1) cause familial and sporadic Paget's disease","volume":"11","author":"Hocking","year":"2002","journal-title":"Hum Molec Genet"}],"container-title":["Journal of Bone and Mineral 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