Torg syndrome is caused by inactivating mutations in MMP2 and is allelic to NAO and Winchester syndrome

Andreas Zankl*, Lauren M Pachman, Andrew K Poznanski, Luisa Bonafé, Fengqiang Wang, Yelena Shusterman, David A. Fishman, Andrea Superti-Furga

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Scopus citations

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. 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.

Original languageEnglish (US)
Pages (from-to)329-333
Number of pages5
JournalJournal of Bone and Mineral Research
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • Autosomal recessive inheritance
  • Matrix metalloproteinase
  • Osteolysis
  • Skeletal dysplasia

ASJC Scopus subject areas

  • Surgery

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