Correlation of Catepsin C gene polymorphisms with Papillon lefevre syndrome in patients referred to oral disease department of dentistry faculty and dermatology department of Sina hospital in Tabriz, Iran

Abstract

Papillon-Lefe`vre syndrome (PLS) is a rare, autosomal recessive disease characterized by palmoplantar keratoderma (PPK) and juvenile periodontitis. The syndrome is believed to affect 1 to 4 persons per million. More than 200 cases have been reported. The immunologic, bacterial and genetic factor appears to be involved in pathogenesis of the disease. Recently genetic defect in PLS has been mapped to chromosome 11q14Eq21, which nvolves mutations of cathepsin C. Regarding the rare occurrence of the syndrome specifically from genetic point of view, we presents the genetic defects in PLS patients in north west of Iran in the present study. Methodology In the present case-control study affected individuals of 4 families from northwest of Iran were evaluated. DNA extraction was performed using the peripheral blood samples prepared from patients and their parents. The suspected mutations in coding sequences of Cathepsin C gene were studied by PCR-RFLP and direct sequencing. The , exact fisher test and odds Ratio (OR) were used to evaluate the correlation of allele and genotypes of CTSC and the disease. Results Two offspring resulting from a consanguineous marriage showed 815GC mutation in homozygous status. The mutation had been occurred in exon 6 of the gene causing the substitution of Argenine with prolin in the amino acid position 272 in related protein. The parent was heterozygous for the mutation. In another family an affected offspring was diagnosed as being homozygous for 628CT mutation. This mutation results in substitution of Argenine with a stop codon in amino acid position 210. The parent in this family were also homozygous for the mutation. The remaining two family did not show any mutation in the coding region of the cathepsin gene. Conclusion The present study indicates that mutation in Cathepsin C gene results in PLS syndrome. Mutation in this gene causes malfunctioning of peptidyl aminopeptidase enzyme, deficiency of immune system and formation of dental plaques in affected individuals. Even though PLS is an extremely rare condition, precise and differential diagnosis of disease can help to effective treatment of the abnormal clinical features