Mutations of the cathepsin C gene are responsible for Papillon-Lefevre syndrome.

Papillon-Lefevre syndrome (PLS) is an autosomal recessive disorder characterised by palmoplantar hyperkeratosis and severe early onset periodontitis that results in the premature loss of the primary and secondary dentitions.
A major gene locus for PLS has been mapped to a 2. 8 cM interval on chromosome 11q14. Correlation of physical and genetic maps of this interval indicate it includes at least 40 ESTs and six known genes including the lysosomal protease cathepsin C gene (CTSC). The CTSC message is expressed at high levels in a variety of immune cells including polymorphonuclear leucocytes, macrophages, and their precursors.
By RT-PCR, we found CTSC is also expressed in epithelial regions commonly affected by PLS, including the palms, soles, knees, and oral keratinised gingiva.
The 4. 7 kb CTSC gene consists of two exons.
Sequence analysis of CTSC from subjects affected with PLS from five consanguineous Turkish families identified four different mutations.
An exon 1 nonsense mutation (856C-- > T) introduces a premature stop codon at amino acid 286. Three exon 2 mutations were identified, including a single nucleotide deletion (2692delA) of codon 349 introducing a frameshift and premature termination codon, a 2 bp deletion (2673-2674delCT) that results in introduction of a stop codon at amino acid 343, and a G-- > A substitution in codon 429 (2931G-- > A) introducing a premature termination codon.
All PLS patients were homozygous for cathepsin C mutations inherited from a common ancestor.
Parents and sibs heterozygous for cathepsin C mutations do not show either the palmoplantar hyperkeratosis or severe early onset periodontitis characteristic of PLS. A more complete understanding of the functional physiology of cathepsin C carries significant implications for understanding normal and abnormal skin development and periodontal disease susceptibility 
