title: Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2.
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.
authors.affiliation: Division of Molecular Pediatrics, Center Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Zankl
authors.forename: L
authors.initials: L
authors.lastname: Bonafé
authors.forename: V
authors.initials: V
authors.lastname: Calcaterra
authors.forename: M
authors.initials: M
authors.lastname: Di Rocco
authors.forename: A
authors.initials: A
authors.lastname: Superti-Furga
mesh_terms: D000328:Adult; D018912:Arabs / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020125:Mutation, Missense; D010014:Osteolysis / Q000235:genetics*
chemical_list: D020778:Matrix Metalloproteinase 2