A novel mutation in PRG4 gene underlying camptodactyly-arthropathy-coxa vara-pericarditis syndrome with the possible expansion of the phenotype to include congenital cataract

BACKGROUND: Camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) is a clinically heterogenous congenital disorder caused by mutations in proteoglycan 4 (PRG4), a chondroitin sulfate proteoglycan that acts as a lubricant for the cartilage surface. Although CACP is a rare genetic disorder, several cases were described in the literature from ethnically different populations including Caucasian, Egyptian, Saudi Arabian, Pakistani, and Korean. We report CACP for the first time in United Arab Emirates. METHODS: Direct sequencing of all the coding exons and splice sites of the PRG4 gene was performed for all the members of the affected family. RESULTS: The studied family is consanguineous and has multiple affected members from different branches showing congenital camptodactyly with arthropathy, the hallmarks of CACP. All the affected family members lack pericarditis, but one of them was born with cataract, which has never been documented in any of the previously reported cases of CACP. Molecular analysis revealed a novel homozygous insertion of a cytosine nucleotide (c.1320dupC) in the highly repetitive portion of the coding sequence of the PRG4 gene. The detected mutation caused a frameshift in the cDNA sequence and created a premature termination codon (p.P440fsX197), which is likely to result in a nonfunctional protein. CONCLUSION: We report a family from the United Arab Emirates with typical features of CACP in whom one of the children had in addition, a bilateral congenital cataract. We also report the identification of a novel null mutation in PRG4 confirming the genetic homogeneity of CACP. Birth Defects Research (Part A) 2012.