CLINICAL AND MOLECULAR ANALYSIS IN PAPILLON-LEFÈVRE SYNDROME

Papillon-Lefevre syndrome (PLS) is a cathepsin C (CTSC)-associated disorder characterized by palmar and plantar hyperkeratosis and aggressively progressing periodontitis. Here we report the clinical and genetic features of 5 PLS patients presenting with a severe periodontal breakdown in primary and permanent dentition, hyperkeratosis over the palms and soles, and recurrent sinusitis and/or tonsillitis. Mutation analysis revealed 2 novel homozygous recessive mutations (c.947 T>C and c.1010 G>C) and 1 previously described homozygous recessive mutation (c.901 G>A), with the parents heterozygous carriers, in 3 families (4 patients). The fourth family presented with the CTSC c.628 C>T heterozygous mutation, which was inherited maternally. The patient carrying the CTSC c.628 C>T mutation featured the classical PLS phenotype, but no PLS clinical characteristics were found in his carrier mother. These findings indicate that both homozygous and heterozygous mutations in the cathepsin C heavy chain domain may lead to the classical PLS phenotype, suggesting roles for epistasis or gene-environment interactions on determination of PLS phenotypes.