Faculty Collaboration Database

CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Nat Genet 1999 Nov;23(3):319-22

Date

11/05/1999

Pubmed ID

10545950

DOI

10.1038/15496

Scopus ID

2-s2.0-0032699840 (requires institutional sign-in at Scopus site)   251 Citations

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.

Author List

Marcelino J, Carpten JD, Suwairi WM, Gutierrez OM, Schwartz S, Robbins C, Sood R, Makalowska I, Baxevanis A, Johnstone B, Laxer RM, Zemel L, Kim CA, Herd JK, Ihle J, Williams C, Johnson M, Raman V, Alonso LG, Brunoni D, Gerstein A, Papadopoulos N, Bahabri SA, Trent JM, Warman ML

Author

Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Base Sequence
Cattle
DNA Mutational Analysis
Female
Genotype
Humans
Hyperplasia
Joint Diseases
Male
Molecular Sequence Data
Mutation
Pericarditis
Phenotype
Proteoglycans
RNA, Messenger
Sequence Homology, Amino Acid
Syndrome
Synovial Membrane