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Torg Syndrome Is Caused by Inactivating Mutations in MMP2 and Is Allelic to NAO and Winchester Syndrome
Author(s) -
Zankl Andreas,
Pachman Lauren,
Poznanski Andrew,
Bonafé Luisa,
Wang Fengqiang,
Shusterman Yelena,
Fishman David A,
SupertiFurga Andrea
Publication year - 2007
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.061013
Subject(s) - medicine , mmp2 , osteolysis , allele , gene mutation , pathology , mutation , genetics , gene , biology , surgery , cancer , metastasis
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. 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. 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. 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.