title: Torg syndrome is caused by inactivating mutations in MMP2 and is allelic to NAO and Winchester syndrome.
abstract: 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.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  We sequenced the MMP2 gene in a patient with clinical and radiographic findings of Torg syndrome. MMP2 activity was measured with gelatin zymography.
  
  
  RESULTS
  Two mutations in the MMP2 gene were identified in this patient. Gelatin zymography indicated complete loss of MMP2 activity.
  
  
  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.
authors.affiliation: CHUV, Lausanne, Switzerland. andreas.zankl@gmail.com
authors.forename: Andreas
authors.initials: A
authors.lastname: Zankl
authors.forename: Lauren
authors.initials: L
authors.lastname: Pachman
authors.forename: Andrew
authors.initials: A
authors.lastname: Poznanski
authors.forename: Luisa
authors.initials: L
authors.lastname: Bonafé
authors.forename: Fengqiang
authors.initials: F
authors.lastname: Wang
authors.forename: Yelena
authors.initials: Y
authors.lastname: Shusterman
authors.forename: David A
authors.initials: DA
authors.lastname: Fishman
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
mesh_terms: D000293:Adolescent; D000483:Alleles; D002648:Child; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D009154:Mutation; D010014:Osteolysis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism; D011859:Radiography; D013577:Syndrome
chemical_list: D020778:Matrix Metalloproteinase 2