Cathepsin C is a lysosomal cysteine protease with an essential role in intracellular and extracellular cleavage of proteins and activation of granular serine proteases expressed in bone marrow-derived cells of myeloid and lymphoid lineage

DOI: 10.1080/00015550510011619 Acta Derm Venereol 86 Papillon-Lefèvre syndrome is an autosomal recessive disorder characterized by palmoplantar hyperkeratosis and aggressive periodontitis. The aim of the study was to identify underlying cathepsin C mutations in 39 subjects with Papillon-Lefèvre syndrome and to explore any phenotypic associations. Genotyping and mutation analyses were performed using standard molecular techniques, and dermatological and oral characteristics were assessed with a semiquantitative clinical score. Three genotypes were present at microsatellite marker D11S1780 and two underlying mutations were identified. The most common genotype (183/183) was associated with an 815G → C mutation in exon 6 resulting in an arginine to proline change at amino acid 272 (R272P). Patients with the 173/173 genotype revealed an exon 7 G300D mutation resulting in a glycine to aspartic acid change at amino acid 300. The mutation in a family with 189/189 genotype remained unknown. A significant difference in hyperkeratosis of the feet was found between the patients with mutations G300D and R272P (p<0.05), but not regarding hands or periodontal condition. Young girls displayed significantly less palmoplantar hyperkeratosis (p<0.05) than young boys. In conclusion, considerable phenotypic heterogeneity was observed within the two cardinal mutations and in the 189/189 genotype.