Novel mutations in PRG4 gene in two Indian families with camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome

Abstract

Background & objectives: Camptodactyly--arthropathy-coxa vara-pericarditis (CACP) syndrome is an autosomal recessive disorder caused by mutations in the PRG4 (proteoglycan 4) gene. Hallmarks of the syndrome include congenital or early-onset camptodactyly and arthropathy with synovial hyperplasia, progressive coxa vara deformity and non-inflammatory pericardial effusions. Till date only around 25 pathogenic mutations have been reported in this gene and none have been reported from India. We report here the mutations in the PRG4 gene in three patients of CACP from two unrelated families from India.

Methods: Molecular genetic studies were done for the three patients with the CACP syndrome, from two unrelated Indian families, through sequence analysis of all coding exons and the exon-intron boundaries of the PRG4 gene.

Results: Two novel frame-shift deletion mutations leading to premature protein termination were found. One patient was identified to be homozygous for a 2 base pair deletion in exon 6 (c.2645_2646delGA) and the two affected siblings from the other family were found to be homozygous for a 4 base pair deletion in exon 6 (c.2883_2886delAAGA).

Conclusions: This is perhaps the first report of PRG4 mutations from India. Further mutation studies in Indian CACP cases will help to determine the mutation spectrum of the PRG4 gene in the Indian population and also help to further elucidate the molecular pathology and the genotype-phenotype correlation of this rare disease.

Fig. 1

(A). Photograph of the knee joints of patient 1b showing bilateral knee joint swelling. (B) Hands of patient 1a showing contractures of the metacarpophalangeal and interphalangeal joints. (C) Elbow radiograph of patient 1a showing widening of the joint space and severe periarticular osteopenia. (D) Knee radiograph of patient 1a showing widening of the joint space and periarticular osteopenia.

Fig. 2 (A & B)

Electropherogram of wild type alleles (top) and mutant alleles (bottom) of patients 1a and 1b and patient 2. The sites of homozygous deletion are indicated by arrows.