title: CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome.
abstract: Altered growth and function of synoviocytes, the intimal cells which line joint cavities and tendon sheaths, occur in a number of skeletal diseases. Hyperplasia of synoviocytes is found in both rheumatoid arthritis and osteoarthritis, despite differences in the underlying aetiologies of the two disorders. We have studied the autosomal recessive disorder camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP; MIM 208250) to identify biological pathways that lead to synoviocyte hyperplasia, the principal pathological feature of this syndrome. Using a positional-candidate approach, we identified mutations in a gene (CACP) encoding a secreted proteoglycan as the cause of CACP. The CACP protein, which has previously been identified as both 'megakaryocyte stimulating factor precursor' and 'superficial zone protein', contains domains that have homology to somatomedin B, heparin-binding proteins, mucins and haemopexins. In addition to expression in joint synovium and cartilage, CACP is expressed in non-skeletal tissues including liver and pericardium. The similarity of CACP sequence to that of other protein families and the expression of CACP in non-skeletal tissues suggest it may have diverse biological activities.
authors.affiliation: Department of Genetics and Center for Human Genetics, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio, USA.
authors.forename: J
authors.initials: J
authors.lastname: Marcelino
authors.forename: J D
authors.initials: JD
authors.lastname: Carpten
authors.forename: W M
authors.initials: WM
authors.lastname: Suwairi
authors.forename: O M
authors.initials: OM
authors.lastname: Gutierrez
authors.forename: S
authors.initials: S
authors.lastname: Schwartz
authors.forename: C
authors.initials: C
authors.lastname: Robbins
authors.forename: R
authors.initials: R
authors.lastname: Sood
authors.forename: I
authors.initials: I
authors.lastname: Makalowska
authors.forename: A
authors.initials: A
authors.lastname: Baxevanis
authors.forename: B
authors.initials: B
authors.lastname: Johnstone
authors.forename: R M
authors.initials: RM
authors.lastname: Laxer
authors.forename: L
authors.initials: L
authors.lastname: Zemel
authors.forename: C A
authors.initials: CA
authors.lastname: Kim
authors.forename: J K
authors.initials: JK
authors.lastname: Herd
authors.forename: J
authors.initials: J
authors.lastname: Ihle
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.forename: M
authors.initials: M
authors.lastname: Johnson
authors.forename: V
authors.initials: V
authors.lastname: Raman
authors.forename: L G
authors.initials: LG
authors.lastname: Alonso
authors.forename: D
authors.initials: D
authors.lastname: Brunoni
authors.forename: A
authors.initials: A
authors.lastname: Gerstein
authors.forename: N
authors.initials: N
authors.lastname: Papadopoulos
authors.forename: S A
authors.initials: SA
authors.lastname: Bahabri
authors.forename: J M
authors.initials: JM
authors.lastname: Trent
authors.forename: M L
authors.initials: ML
authors.lastname: Warman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D007592:Joint Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010493:Pericarditis / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011509:Proteoglycans / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013577:Syndrome; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology
chemical_list: D011509:Proteoglycans; D012333:RNA, Messenger