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

A. Zankl, L. Bonafé, V. Calcaterra, M. Di Rocco, Andrea Superti-Furga

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)261-266
Number of pages6
JournalClinical Genetics
Volume67
Issue number3
DOIs
Publication statusPublished - Mar 2005

Keywords

  • Chondrodysplasia
  • Metallo-proteinase
  • NAO syndrome
  • Osteolysis
  • Skeletal dysplasia
  • Torg syndrome

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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