Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2

Clin Genet. 2005 Mar;67(3):261-6. doi: 10.1111/j.1399-0004.2004.00402.x.


The inherited osteolysis syndromes are a heterogeneous group of skeletal disorders whose classification is still uncertain. Three osteolysis syndromes show autosomal recessive inheritance and multicentric involvement: Torg syndrome (OMIM 259600), Winchester syndrome (OMIM 277950) and Nodulosis-Arthropathy-Osteolysis syndrome (NAO; OMIM 605156). The 2001 Nosology of the International Skeletal Dysplasia Society (Hall CM, Am J Med Genet 2002: 113: 65) classifies NAO as a variant of Torg syndrome, while Winchester syndrome is considered as a separate disorder. Recently, mutations in the matrix metalloproteinase 2 (MMP2) gene were identified in affected individuals with a clinical diagnosis of NAO in two Arab families. We report a homozygous missense mutation (E404K) in the active site of MMP2 in a 21-year-old woman with a severe form of osteolysis best compatible with a diagnosis of Winchester syndrome. The clinical and molecular findings suggest that Torg, NAO and Winchester syndromes are allelic disorders that form a clinical spectrum.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arabs / genetics
  • DNA Mutational Analysis
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / genetics*
  • Mutation, Missense
  • Osteolysis / genetics*


  • Matrix Metalloproteinase 2