Demonstration of altered splicing with the IVS3-1G --> a mutation of cathepsin C

Papillon-Lefèvre syndrome is an autosomal recessive palmoplantar keratoderma caused by cathepsin C gene mutations. We present the second family segregating the IVS3-1G --> A mutation and demonstrate for the first time that altered splicing and decreased enzymatic activity occur. RNA analysis revealed two species in carriers, corresponding to wild-type and mutant transcripts, and only the mutant transcript in affected individuals. Sequencing of the mutant transcript revealed that it lacked exon 3, resulting in a frameshift and introduction of a premature termination codon.