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.
- Autosomal recessive inheritance
- Matrix metalloproteinase
- Skeletal dysplasia
ASJC Scopus subject areas