{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:54:32Z","timestamp":1793829272924,"version":"4.6.1"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2007,2,1]],"date-time":"2007-02-01T00:00:00Z","timestamp":1170288000000},"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":[[2007,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Torg syndrome is a multicentric osteolysis syndrome of unknown etiology. We identified mutations in the MMP2 gene in a patient with Torg syndrome that resulted in complete loss of MMP2 activity. MMP2 mutations were previously identified in patients with NAO and Winchester syndrome. Our findings suggest that Torg, NAO, and Winchester syndrome are allelic disorders.<\/jats:p>\n               <jats:p>Introduction: Torg, nodulosis-arthropathy-osteolysis (NAO), and Winchester syndrome are a group of autosomal recessive osteolysis syndromes with marked clinical and radiological overlap. It has been suggested that the three conditions are causally related, but molecular evidence for this assumption has been lacking. Recently, mutations in the matrix metalloproteinase 2 gene (MMP2) have been reported in patients with NAO and Winchester syndrome.<\/jats:p>\n               <jats:p>Materials and Methods: We sequenced the MMP2 gene in a patient with clinical and radiographic findings of Torg syndrome. MMP2 activity was measured with gelatin zymography.<\/jats:p>\n               <jats:p>Results: Two mutations in the MMP2 gene were identified in this patient. Gelatin zymography indicated complete loss of MMP2 activity.<\/jats:p>\n               <jats:p>Conclusions: Torg, NAO, and Winchester syndrome are allelic disorders. The name Torg-Winchester syndrome is suggested as a common denominator for this group of disorders.<\/jats:p>","DOI":"10.1359\/jbmr.061013","type":"journal-article","created":{"date-parts":[[2006,10,24]],"date-time":"2006-10-24T13:28:47Z","timestamp":1161696527000},"page":"329-333","source":"Crossref","is-referenced-by-count":65,"title":["Torg Syndrome Is Caused by Inactivating Mutations in <i>MMP2<\/i> and Is Allelic to NAO and Winchester Syndrome"],"prefix":"10.1093","volume":"22","author":[{"given":"Andreas","family":"Zankl","sequence":"first","affiliation":[{"name":"Queensland Clinical Genetics Service, Royal Children's Hospital, Brisbane, Australia"},{"name":"Division of Molecular Pediatrics, CHUV, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Pachman","sequence":"additional","affiliation":[{"name":"Northwestern University's Feinberg School of Medicine, Molecular and Cellular Pathobiology Program, The Children's Memorial Research Center, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Poznanski","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, The Children's Memorial Hospital, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Bonaf\u00e9","sequence":"additional","affiliation":[{"name":"Division of Molecular Pediatrics, CHUV, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena","family":"Shusterman","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A","family":"Fishman","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, New York University School of Medicine, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Superti-Furga","sequence":"additional","affiliation":[{"name":"Centre for Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany"},{"name":"Division of Molecular Pediatrics, CHUV, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,4]]},"reference":[{"key":"2024020319334016800_bib1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/ajmg.10828","article-title":"International nosology and classification of constitutional disorders of bone (2001)","volume":"113","author":"Hall","year":"2002","journal-title":"Am J Med Genet"},{"key":"2024020319334016800_bib2","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/(SICI)1096-8628(19981116)80:3<207::AID-AJMG5>3.0.CO;2-A","article-title":"Torg osteolysis syndrome","volume":"80","author":"Eisenstein","year":"1998","journal-title":"Am J Med Genet"},{"key":"2024020319334016800_bib3","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0022-3476(69)80395-1","article-title":"Hereditary multicentric osteolysis with recessive transmission: A new syndrome","volume":"75","author":"Torg","year":"1969","journal-title":"J Pediatr"},{"key":"2024020319334016800_bib4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/1096-8628(20000703)93:1<11::AID-AJMG3>3.0.CO;2-3","article-title":"Inherited multicentric osteolysis with arthritis: A variant resembling Torg syndrome in a Saudi family","volume":"93","author":"Al Aqeel","year":"2000","journal-title":"Am J Med Genet"},{"key":"2024020319334016800_bib5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/1096-8628(20000703)93:1<5::AID-AJMG2>3.0.CO;2-Y","article-title":"New form of idiopathic osteolysis: Nodulosis, arthropathy and osteolysis (NAO) syndrome","volume":"93","author":"Al-Mayouf","year":"2000","journal-title":"Am J Med Genet"},{"key":"2024020319334016800_bib6","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00247-001-0649-4","article-title":"Radiological findings in NAO syndrome","volume":"32","author":"Al-Otaibi","year":"2002","journal-title":"Pediatr Radiol"},{"key":"2024020319334016800_bib7","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/0030-4220(92)90363-U","article-title":"Winchester syndrome. A case report and literature review","volume":"74","author":"Prapanpoch","year":"1992","journal-title":"Oral Surg Oral Med Oral Pathol"},{"key":"2024020319334016800_bib8","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2214\/ajr.106.1.121","article-title":"A new acid mucopolysaccharidosis with skeletal deformities simulating rheumatoid arthritis","volume":"106","author":"Winchester","year":"1969","journal-title":"Am J Roentgenol Radium Ther Nucl Med"},{"key":"2024020319334016800_bib9","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1136\/jmg.26.12.772","article-title":"Winchester's syndrome","volume":"26","author":"Winter","year":"1989","journal-title":"J Med Genet"},{"key":"2024020319334016800_bib10","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1399-0004.2004.00402.x","article-title":"Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2","volume":"67","author":"Zankl","year":"2005","journal-title":"Clin Genet"},{"key":"2024020319334016800_bib11","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/90100","article-title":"Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome","volume":"28","author":"Martignetti","year":"2001","journal-title":"Nat Genet"},{"key":"2024020319334016800_bib12","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1399-0004.2006.00584.x","article-title":"A novel homozygous MMP2 mutation in a family with Winchester syndrome","volume":"69","author":"Rouzier","year":"2006","journal-title":"Clin Genet"},{"key":"2024020319334016800_bib13","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/ijc.20697","article-title":"Matrilysin (MMP-7) promotes invasion of ovarian cancer cells by activation of progelatinase","volume":"114","author":"Wang","year":"2005","journal-title":"Int J Cancer"},{"key":"2024020319334016800_bib14","doi-asserted-by":"crossref","first-page":"5578","DOI":"10.1073\/pnas.87.14.5578","article-title":"The cysteine switch: A principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family","volume":"87","author":"Van Wart","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024020319334016800_bib15","doi-asserted-by":"crossref","first-page":"5730","DOI":"10.1021\/bi00319a011","article-title":"An interactive computer graphics study of thermolysin-catalyzed peptide cleavage and inhibition by N-carboxymethyl dipeptides","volume":"23","author":"Hangauer","year":"1984","journal-title":"Biochemistry"},{"key":"2024020319334016800_bib16","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1126\/science.284.5420.1667","article-title":"Structure of human pro-matrix metalloproteinase-2: Activation mechanism revealed","volume":"284","author":"Morgunova","year":"1999","journal-title":"Science"},{"key":"2024020319334016800_bib17","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1172\/JCI10158","article-title":"Osteocyte and osteoblast apoptosis and excessive bone deposition accompany failure of collagenase cleavage of collagen","volume":"106","author":"Zhao","year":"2000","journal-title":"J Clin Invest"},{"key":"2024020319334016800_bib18","doi-asserted-by":"crossref","first-page":"22389","DOI":"10.1074\/jbc.272.36.22389","article-title":"Unaltered secretion of beta-amyloid precursor protein in gelatinase A (matrix metalloproteinase 2)-deficient mice","volume":"272","author":"Itoh","year":"1997","journal-title":"J Biol Chem"},{"key":"2024020319334016800_bib19","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0092-8674(00)80064-1","article-title":"MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover","volume":"99","author":"Holmbeck","year":"1999","journal-title":"Cell"},{"key":"2024020319334016800_bib20","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1101\/gad.14.2.163","article-title":"Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis","volume":"14","author":"Yu","year":"2000","journal-title":"Genes Dev"},{"key":"2024020319334016800_bib21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/79128","article-title":"Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease","volume":"26","author":"Kinoshita","year":"2000","journal-title":"Nat Genet"},{"key":"2024020319334016800_bib22","doi-asserted-by":"crossref","first-page":"7718","DOI":"10.1074\/jbc.M208857200","article-title":"Transforming growth factor-beta 1 mutations in Camurati-Engelmann disease lead to increased signaling by altering either activation or secretion of the mutant protein","volume":"278","author":"Janssens","year":"2003","journal-title":"J Biol Chem"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1359%2Fjbmr.061013","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/22\/2\/329\/56552888\/5650220217.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/22\/2\/329\/56552888\/5650220217.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:47:54Z","timestamp":1710341274000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/22\/2\/329-333\/7597394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,2,1]]},"references-count":22,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2009,12,4]]},"published-print":{"date-parts":[[2007,2,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.061013","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2007,2,1]]},"published":{"date-parts":[[2007,2,1]]}}}