Nature Genetics
23, 319 - 322 (1999)
doi:10.1038/15496
CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa
vara-pericarditis syndromeJose Marcelino1, 15, John D. Carpten2, 15, Wafaa M. Suwairi1, 4, 5, Orlando M. Gutierrez1, Stuart Schwartz1, Christiane Robbins2, Raman Sood2, Izabela Makalowska2, 3, Andy Baxevanis3, Brian Johnstone6, Ronald M. Laxer7, Lawrence Zemel8, Chong Ae Kim9, J. Kenneth Herd10, Johannes Ihle11, Cal Williams12, Mark Johnson12, Vidya Raman12, Luís Garcia Alonso13, Decio Brunoni13, Amy Gerstein14, Nickolas Papadopoulos14, Sultan A. Bahabri5, Jeffrey M. Trent2
& Matthew L. Warman11
Department of Genetics and Center for Human Genetics,
Case Western Reserve University and University Hospitals of Cleveland,
Cleveland, Ohio, USA. 2
Cancer Genetics Branch, National Human Genome Research
Institute, National Institutes of Health, Bethesda,
Maryland, USA. 3
Genome Technology Branch, National Human Genome Research
Institute, National Institutes of Health, Bethesda,
Maryland, USA. 4
Department of Pediatrics, Riyadh Armed Forces Hospital, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. 5
Department of Pediatrics, King Faisal Specialist Hospital
and Research Center, Riyadh, Saudi Arabia. 6
Department of Orthopaedics, Case Western Reserve University
and University Hospitals of Cleveland, Cleveland, Ohio
, USA. 7
Division of Rheumatology and Department of Pediatrics,
The Hospital for Sick Children and the University of Toronto,
Toronto, Canada. 8
Division of Rheumatology, Newington Children's Hospital
, Hartford, Connecticut, USA. 9
Department of Genetics, University of São Paolo
, São Paolo, Brazil. 10
Department of Pediatrics, East Tennessee State University,
James H. Quillen College of Medicine, Johnson City,
Tennessee, USA. 11
Division of Rheumatology, University Children's Hospital
, Tuebingen, Germany. 12
Department of Pediatrics, Washington University and
St. Louis Children's Hospital, St. Louis, Missouri,
USA. 13
Medical Genetics Institute, São Paulo Federal
University-Paulista School of Medicine, São Paulo,
Brazil. 14
Institute of Cancer Genetics, Department of Pathology,
Columbia University, New York, New York, USA
. 15
These authors contributed equally to this work.
Correspondence should be addressed to Matthew L. Warman mlw14@po.cwru.edu or Jeffrey M. Trent jtrent@nhgri.nih.govAltered growth and function of synoviocytes, the intimal cells which line
joint cavities and tendon sheaths, occur in a number of skeletal diseases1. 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'2 and 'superficial zone protein'3, 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.
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