Abstract
Camptodactyly-Arthropathy-Coxa vara-Pericarditis (CACP) syndrome is a rare autosomal recessive disorder caused by mutations in PRG4 gene that encodes for proteoglycan 4, a mucin-like glycoprotein that is the major lubricant for joints and tendon surfaces. The molecular studies reported so far have described the identification of 15 mutations associated with this syndrome and the majority of them were found in families of Arabian origin. Here we report the molecular investigation of the largest European cohort that comprises 13 patients, and allowed the identification of 5 novel mutations and of the first case of CACP syndrome resulting from uniparental disomy of chromosome 1.
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Bahabri SA, Suwairi WM, Laxer RM, Polinkovsky A, Dalaan AA, Warman ML : The camptodactyly-arthropathy-coxa vara-pericarditis syndrome: clinical features and genetic mapping to human chromosome 1. Arthritis Rheum 1998; 41: 730–735.
Martinez-Lavin M, Buendia A, Delgado E et al: A familial syndrome of pericarditis, arthritis, and camptodactyly. New Engl J Med 1983; 309: 224–225.
Bulutlar G, Yazici H, Ozdogan H, Schreuder I : A familial syndrome of pericarditis, arthritis, camptodactyly, and coxa vara. Arthritis Rheum 1986; 29: 436–438.
Marcelino J, Carpten JD, Suwairi WM et al: CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Nat Genet 1999; 23: 319–322.
Ikegawa S, Sano M, Koshizuka Y, Nakamura Y : Isolation, characterization and mapping of the mouse and human PRG4 (proteoglycan 4) genes. Cytogenet Cell Genet 2000; 90: 291–297.
Jay GD, Britt DE, Cha CJ : Lubricin is a product of megakaryocyte stimulating factor gene expression by human synovial fibroblasts. J Rheumatol 2000; 27: 594–600.
Rees SG, Davies JR, Tudor D et al: Immunolocalisation and expression of proteoglycan 4 (cartilage superficial zone proteoglycan) in tendon. Matrix Biol 2002; 21: 593–602.
Rhee DK, Marcelino J, Baker M et al: The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. J Clin Invest 2005; 115: 622–631.
Coles JM, Zhang L, Blum JJ et al: Loss of cartilage structure, stiffness, and frictional properties in mice lacking PRG4. Arthritis Rheum 2010; 62: 1666–1674.
Jay GD, Harris DA, Cha CJ : Boundary lubrication by lubricin is mediated by O-linked beta(1-3)Gal-GalNAc oligosaccharides. Glycoconj J 2001; 18: 807–815.
Jay GD : Characterization of a bovine synovial fluid lubricating factor. I. Chemical, surface activity and lubricating properties. Connect Tissue Res 1992; 28: 71–88.
Alazami AM, Al-Mayouf SM, Wyngaard CA, Meyer B : Novel PRG4 mutations underlie CACP in Saudi families. Hum Mutat 2006; 27: 213.
Basit S, Iqbal Z, Umicevic-Mirkov M et al: A novel deletion mutation in proteoglycan-4 underlies camptodactyly-arthropathy-coxa-vara-pericarditis syndrome in a consanguineous pakistani family. Arch Med Res 2011; 42: 110–114.
Akawi NA, Ali BR, Al-Gazali L : A novel mutation in PRG4 gene underlying camptodactyly-arthropathy-coxa vara-pericarditis syndrome with the possible expansion of the phenotype to include congenital cataract. Birth Defects Res A Clin Mol Teratol 2012; 94: 553–556.
Rozen S, Skaletsky H : Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 2000; 132: 365–386.
Livak KJ, Schmittgen TD : Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402–408.
Reese MG, Eeckman FH, Kulp D, Haussler D : Improved splice site detection in Genie. J Comp Biol 1997; 4: 311–323.
Hebsgaard SM, Korning PG, Tolstrup N, Engelbrecht J, Rouze P, Brunak S : Splice site prediction in Arabidopsis thaliana DNA by combining local and global sequence information. Nucleic Acids Res 1996; 24: 3439–3452.
Brunak S, Engelbrecht J, Knudsen S : Prediction of human mRNA donor and acceptor sites from the DNA sequence. J Mol Biol 1991; 220: 49–65.
Rhee DK, Marcelino J, Al-Mayouf S et al: Consequences of disease-causing mutations on lubricin protein synthesis, secretion, and post-translational processing. J Biol Chem 2005; 280: 31325–31332.
Albuhairan I, Al-Mayouf SM : Camptodactyly-arthropathy-coxavara-pericarditis syndrome in Saudi Arabia: Clinical and molecular genetic findings in 22 patients. Semin Arthritis Rheum 2013, (in press).
Nimmo G, Monsonego S, Descartes M, Franklin J, Steinberg S, Braverman N : Rhizomelic chrondrodysplasia punctata type 2 resulting from paternal isodisomy of chromosome 1. Am J Med Genet A 2010; 152A: 1812–1817.
Richette P, Bardin T, Stheneur C : Achondroplasia: from genotype to phenotype. Joint Bone Spine 2008; 75: 125–130.
Acknowledgements
We are grateful to all the patients and their parents for their kind cooperation. This work was supported by the Italian Ministry for University (MIUR; ex-60%) to EG.
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Ciullini Mannurita, S., Vignoli, M., Bianchi, L. et al. CACP syndrome: identification of five novel mutations and of the first case of UPD in the largest European cohort. Eur J Hum Genet 22, 197–201 (2014). https://doi.org/10.1038/ejhg.2013.123
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DOI: https://doi.org/10.1038/ejhg.2013.123
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