Description of two new cathepsin C gene mutations in patients with Papillon-Lefèvre syndrome

Papillon-Lefèvre syndrome (PLS) is a rare autosomal disorder characterized by severe periodontitis and palmar plantar hyperkeratosis (PPK). PLS is caused by mutations in the cathepsin C (CTSC) gene. Dipeptidyl peptidase I (DPPI) encoded by the CTSC locus removes dipeptides from the amino terminus of the protein substrate and mainly plays an important role in immune and inflammatory processes. Several mutations have been reported in this gene in patients with PLS. This study reports two novel deletion mutation of the CTSC gene in two Indian families with PLS.

Peripheral blood samples were obtained for genomic DNA isolation from individuals belonging to two Indian families. Exon-specific intronic primers were used to amplify DNA from all individuals, and the PCR products were subsequently sequenced to detect the mutations. Heteroduplex analysis (HDA) was used to confirm heterozygosity and to determine the presence of mutations in control individuals.

All patients from both families had a classic PLS phenotype, which included PPK and severe periodontitis. Sequence analysis of the CTSC gene revealed two novel deletion mutations, one (1213-1215delCAT) in exon 7 and the other (629-630delGA) in exon 4 of the CTSC gene. For both mutations, the patients were homozygous, whereas the parents were heterozygous.

This study reports two novel deletion mutations in two Indian families with PLS. One of the mutations introduces a premature stop codon, thereby producing a truncated protein. In the other case, the mutation observed leads to the loss of a highly conserved histidine molecule that is present in the active site of the enzyme. In both cases, mutations may result in a conformation change, causing loss of the enzymatic activity.