A novel nonsense mutation in cathepsin C gene in an Egyptian patient presenting with Papillon–Lefèvre syndrome

Background Cathepsin C gene (CTSC) (MIM#602365) is a lysosomal cysteine proteinase coding gene which encodes for CTSC protein that plays a major role in the activation of granule serine proteases, particularly leukocyte elastase and granzymes A and B. This activity was proposed to play a role in epithelial differentiation and desquamation. Mutations that cause Disruption in the CTSC expression or function will result in loss of immunological response such as defects of phagocytic function and deregulation of localized polymorphonuclears response with subsequent clinical manifestation. Aim The aim of this study is to detect the mutation in CTSC gene expected to be the cause of Papillon Lefèvre syndrome (PLS) in an Egyptian patient clinically diagnosed as PLS and to characterize the clinical features. Patient and methods A 5 year and 3 month old girl from the outpatient’s Oro-Dental Genetics clinic – National Research Center presented with the typical clinical findings of Papillon Lefevre syndrome. Genomic DNA was extracted from peripheral blood samples of the patient, her parents and 20 healthy Egyptian controls using standard procedures. All exons of the CTSC gene were amplified by PCR. Sequence analysis of the patient, her parents and controls was performed for mutation detection. Results Mutation analysis of the CTSC gene in our patient revealed a novel homozygous nonsense mutation in exon 5 (W237X). Her parents revealed the presence of the same mutation in a heterozygous state. The 20 controls showed only the wild type sequence of all exons (no mutation). Conclusion This study reported a novel nonsense mutation in the CTSC gene in an Egyptian patient. This novel nonsense mutation is predicted to produce truncated dipeptidyl-peptidase1 causing PLS phenotype in this patient