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.
ABSTRACT
Total collagen content in heart decreased significantly till day 8 of dexamethasone (Dex: 2.5 mg/kg week; s.c. for 2 weeks) treatment and increased on withdrawal of Dex. Acid soluble collagen content in heart decreased till day 12 of Dex treatment, reached normal level on day 16 of Dex treatment and exhibited an increase thereafter. Pepsin solubilized fraction in heart also behaved similarly as the acid soluble fraction, but reached normal level on Dex withdrawal. The total collagen content and the acid soluble collagen in kidney decreased significantly throughout treatment as well as on Dex withdrawal whereas, the pepsin solubilized collagen fraction in kidney exhibited a significant increase from day 8 of Dex treatment and the level was maintained throughout the experiment. Incorporation of 14C-proline in both, heart and kidney was found to be reduced. Electrophoretic pattern of pepsin collagen solubilized fraction of heart and kidney revealed alterations in subunit composition and its types on Dex administration and withdrawal. Thus, administration of Dex induced alterations in the metabolism of collagen and on Dex withdrawal, the system slowly tended to attain normalcy.