Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Novel Mutations of Camptodactyly Arthropathy Coxa Vara Pericarditis (CACP) Syndrome: A Study on Ten Cases.
Mannurita7, Sara Ciullini, Vignoli7, Marina, Bianchi7, Lucia, Azzari7, Chiara, de Martino7, Maurizio, Ravelli4, Angelo, Kondi6, Anuela
Department of BioMedicine, Section of Rheumatology, Transition Clinic, University of Florence
Department of Pediatrics, Leiden University Medical Centre, The Netherlands
Department of Pediatrics, University of Chieti, Chieti, Italy
Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini and Università degli Studi di Genoa
Istituto G. Pini, Milan, Italy
Pediatric Department, University Hospital Centre, Tirana, Albania
University of Florence, Department of Sciences for Woman and Child's Health
The Camptodactyly Arthropathy Coxa vara Pericarditis (CACP) syndrome is an autosomal recessive disease characterised by congenital camptodactyly, no inflammatory arthropathy, joint failure, synovial hyperplasia, coxa vara, and thickening of the pericardium. The causative gene for CACP is PRG4 that is located on chromosome band 1q2531 and consists of 12 exons. It encodes for a mucin-like glycoprotein named "proteoglycan-4" (PRG-4) which acts as the major surface lubricant for joints and tendons.
1.To investigate possible genomic alteration in patients with clinical manifestations of CACP. 2.To perform a comprehensive analysis of the PRG-4 gene.
Patients and Methods:
Six unrelated patients and two pairs of siblings (2 sisters, 1 sister,1 brother) with a phenotype resembling CACP syndrome were referred to us for mutational analysis of PRG-4 gene. The age of onset was mainly at birth (median age at diagnosis 5.5 years). Genomic DNA was extracted by peripheral blood and polymerase chain reaction was performed to amplify PRG-4 exon sequences including intro-exon boundaries using specific primers. The coding regions were sequenced, with the exception of 800bp, within exon 6 due to highly repetitive motifs.
Six novel homozygous mutations within CACP gene were identified in seven patients. The 2 sisters harboured the same nonsense alteration (Y1216X) that cause a frame-shift that creates a premature stop signal leading to the production of a truncated protein. Four mutations were small deletions of 1bp, 2bp and 5bp, three of which located within exon 6. These deletions cause frame-shift mutations and create a premature stop codon. In the remaining patients, we detected one substitution affecting the donor splice site (IVS8+3A>G); the bioinformatics analysis of this alteration predicts a decrease of the strength of the new splice site sequence that could be responsible for an aberrant splicing of the premature transcript. The analysis of CACP protein would be necessary to test the predicted effect of the mutations.
CACP syndrome is a rare disorder often misdiagnosed with other paediatric connective tissue diseases. This is the first study analysing the largest PRG-4 coding region, and it allowed identifying a new set of molecular aberrations associated with the occurrence of CACP syndrome.
To cite this abstract, please use the following information:
Mannurita, Sara Ciullini, Vignoli, Marina, Bianchi, Lucia, Azzari, Chiara, de Martino, Maurizio, Ravelli, Angelo, et al; Novel Mutations of Camptodactyly Arthropathy Coxa Vara Pericarditis (CACP) Syndrome: A Study on Ten Cases. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :261