Phenotypic variation and allelic heterogeneity in young patients with Papillon-Lefèvre syndrome.

[papillon-lefèvre syndrome]

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 D 11 S 1780 and two underlying mutations were identified . The most common genotype (183 /183 ) was associated with an 815 G --> C mutation in exon 6 resulting in an arginine to proline change at amino acid 272 (R 272 P ). Patients with the 173 /173 genotype revealed an exon 7 G 300 D 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 G 300 D and R 272 P ( 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 .