title: A novel matrix metalloproteinase 2 (MMP2) terminal hemopexin domain mutation in a family with multicentric osteolysis with nodulosis and arthritis with cardiac defects.
abstract: Multicentric osteolysis with nodulosis and arthropathy (MONA, NAO (OMIM no. 605156)) is an autosomal recessive member of the 'vanishing bone' syndromes and is notable for the extent of carpal and tarsal osteolysis and interphalangeal joint erosions, facial dysmorphia, and the presence of fibrocollagenous nodules. This rare disorder has been described previously in Saudi Arabian and Indian families. We now report on the first Turkish family with MONA, further confirming the panethnic nature of this disease. Strikingly, and in addition to the previously noted skeletal and joint features, affected members of this family also had congenital heart defects. Molecular analysis identified a novel MMP2 inactivating mutation that deletes the terminal hemopexin domains and thus confirmed the diagnosis of MONA. On the basis of these findings, we suggest that cardiac defects may also represent a component of this syndrome and thus a physiologically relevant target of MMP-2 activity.
authors.affiliation: Department of Pediatrics, Division of Genetics,Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey.
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tuysuz
authors.forename: Rebecca
authors.initials: R
authors.lastname: Mosig
authors.forename: Gürkan
authors.initials: G
authors.lastname: Altun
authors.forename: Selim
authors.initials: S
authors.lastname: Sancak
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Glucksman
authors.forename: John A
authors.initials: JA
authors.lastname: Martignetti
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D001168:Arthritis / Q000473:pathology*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D031845:Hajdu-Cheney Syndrome / Q000473:pathology*; D006330:Heart Defects, Congenital / Q000473:pathology; D006466:Hemopexin / Q000378:metabolism; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D017434:Protein Structure, Tertiary; D013577:Syndrome; D014421:Turkey
chemical_list: D006466:Hemopexin; D020778:Matrix Metalloproteinase 2