Novel PRG4 mutations underlie CACP in Saudi families

The camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is an autosomal recessive disorder caused by mutations in the PRG4 (Proteoglycan 4) gene. Manifestations vary across families as well as between affected individuals from the same family, with camptodactyly and arthropathy of the knees the most ubiquitous, while pericarditis is evident in only one-fifth of all reported cases. Thus far only eight pathogenic mutations have been described in this gene. We examined seven newly diagnosed childhood patients of this syndrome, hailing from four unrelated families of Saudi origin. Five novel mutations were uncovered, including four frameshift deletions and one nonsense mutation (c.923_924delAA, c.3125_3128delGAGT, c.3139_3140delAA, c.3276_3277delAA, c.4078A>T). No genotype/phenotype association was observed. Because all mutations reported in CACP patients thus far predict premature truncation, we hypothesize that missense mutations are either not physiologically relevant, or that they trigger a clinical phenotype that is distinct from classical CACP. This is only the second published communication on PRG4 mutations, and increases the number of reported mutations for all ethnicities from 8 to 13, and for the Arab population specifically from one to six.