A Novel Deletion Mutation in Proteoglycan-4 Underlies Camptodactyly-Arthropathy-Coxa-Vara-Pericarditis Syndrome in a Consanguineous Pakistani Family

Background and AimsCamptodactyly-arthropathy-coxa-vara-pericarditis (CACP) syndrome is an autosomal recessive condition that mostly affects joints and tendons but can also affect the pericardium, which is a surface surrounding the heart. CACP syndrome is caused by mutations in a secreted proteoglycan 4 (PRG4) gene, which expresses in skeletal as well as nonskeletal tissues. We undertook this study to genetically screen a large consanguineous Pakistani family segregating CACP in an autosomal recessive manner.MethodsGenome-wide homozygosity mapping of 10 members of a Pakistani family including six affected and four normal individuals was carried out using 250K SNP genotyping array. To screen for mutation in PRG4 gene, all coding exons and exon-intron junctions were sequenced using ABI prism 3730 automated DNA sequencer.ResultsGenome-wide homozygosity mapping revealed a large homozygous region on chromosome 1 carried by all the affected individuals. This region contains the previously described PRG4 gene involved in CACP syndrome. Sequence analysis of PRG4 gene in affected individuals of the family presented here revealed a 2 base-pair (bp) deletion (c.2816_2817delAA) predicting a frame shift mutation (p.Lys939fsX38). To our knowledge, this is probably the first mutation identified in PRG4 gene in a Pakistani family.ConclusionsWe described a 2-bp novel deletion mutation in PRG4 gene in a Pakistani family with CACP. Our findings extend the body of evidence that only nonsense mutation in PRG4 gene triggers the phenotype.