AB0908 A Novel Mutation in Proteoglycan-4 Underlies Camptodactyly-Arthropathy-Coxa-Vara-Pericarditis Syndrome in A Chinese Family

Background Camptodactyly-arthropathy-coxa-vara-pericarditis (CACP) syndrome is an autosomal recessive condition characterized by the association of congenital or early onset camptodactyly and noninflammatory arthropathy, it can also affect the pericardium. CACP syndrome is caused by mutations in proteoglycan 4 (PRG4), a chondroitin sulfate proteoglycan that acts as a lubricant for the cartilage surface. Several cases were described in the literature from ethnically different populations including Caucasian, Egyptian, Saudi Arabian, Pakistani, Indian and Korean. Objectives We undertook this study to genetically screen a Chinese family segregating CACP in an autosomal recessive manner. Methods To screen for mutation in PRG4 gene, all coding exons and exon-intron junctions were sequenced using ABI prism 3730 automated DNA sequencer. Results Sequence analysis of PRG4 gene in affected individual of the family presented here revealed one base insertion (exon 9, c.3755_3756insT) predicting a frame shift mutation (p.Lys1253fs*1). Sequencing of PRG4 exon 9 in the parents showed that the father was a heterozygous carrier of the c.3755_3756insT mutation, but the mother did not have this alteration. To our knowledge, this is probably the first mutation identified in PRG4 gene in Chinese population. Conclusions We described a novel insertion mutation in PRG4 gene in a Chinese family with CACP. References 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. CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Nature genetics 1999, 23 (3), 319–22. Choi BR, Lim YH, Joo KB, Paik SS, Kim NS, Lee JK, Yoo DH. Camptodactyly, arthropathy, coxa vara, pericarditis (CACP)syndrome: a case report. Journal of Korean medical science 2004, 19 (6), 907–10. Basit S, Iqbal Z, Umicevic-Mirkov M, Kamran Ul-Hassan Naqvi S, Coenen M, Ansar M, van Bokhoven H, Ahmad W. A novel deletion mutation in proteoglycan-4 underlies camptodactyly-arthropathy-coxa-vara-pericarditis syndrome in a consanguineous pakistani family. Archives of medical research 2011, 42 (2), 110–4. 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 research. Part A, Clinical and molecular teratology 2012, 94 (7), 553–6. Nandagopalan RS, Phadke SR, Dalal AB, Ranganath P. Novel mutations in PRG4 gene in two Indian families with camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome. The Indian journal of medical research 2014, 140 (2), 221–6. Ciullini Mannurita S, Vignoli M, Bianchi L, Kondi A, Gerloni V, Breda L, Ten Cate R, Alessio M, Ravelli A, Falcini F, Gambineri E. CACP syndrome: identification of five novel mutations and of the first case of UPD in the largest European cohort. European journal of human genetics: EJHG 2014, 22 (2), 197–201 Disclosure of Interest None declared