Phenotypic variation and allelic heterogeneity in young patients with 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 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.
Ullbro
Christer
C
Department of Dentistry, King Faisal Specialist Hospital, Research Centre, Riyadh, Saudi Arabia. cullbro@hotmail.com
El-Samadi
Safia
S
Boumah
Christine
C
Al-Yousef
Nujoud
N
Wakil
Salma
S
Twetman
Svante
S
Alfadley
Abdullah
A
Thestrup-Pedersen
Kristian
K
Meyer
Brian
B
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D020789:Cathepsin C / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D018740:Genetic Heterogeneity; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010214:Papillon-Lefevre Disease / Q000235:genetics*; D010641:Phenotype; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D012737:Sex Factors
D020789:Cathepsin C