Functional Cathepsin C mutations cause different Papillon-Lefèvre syndrome phenotypes.
OBJECTIVE
The autosomal-recessive Papillon-Lefèvre syndrome (PLS) is characterized by severe aggressive periodontitis, combined with palmoplantar hyperkeratosis, and is caused by mutations in the Cathepsin C (CTSC) gene. This study aimed to identify CTSC mutations in different PLS phenotypes, including atypical forms and isolated pre-pubertal aggressive periodontitis (PAP).


METHODS
Thirteen families with different phenotypes were analysed by direct sequencing of the entire coding region and the regulatory regions of CTSC. The function of novel mutations was tested with enzyme activity measurements.


RESULTS
In 11 of 13 families, 12 different pathogenic CTSC mutations were found in 10 typical PLS patients, three atypical cases and one PAP patient. Out of four novel mutations, three result in protein truncation and are thus considered to be pathogenic. The homozygous c.854C>T nucleotide exchange (p.P285L) was associated with an almost complete loss of enzyme activity. The observed phenotypic heterogeneity could not be associated with specific genotypes.


CONCLUSIONS
The phenotypic variability of the PLS associated with an identical genetic background may reflect the influence of additional genetic or environmental factors on disease characteristics. CTSC mutation analyses should be considered for differential diagnosis in all children suffering from severe aggressive periodontitis.
Noack
Barbara
B
Department of Conservative Dentistry, University Hospital Carl Gustav Carus, TU Dresden, Germany. Barbara.Noack@uniklinikum-dresden.de
Görgens
Heike
H
Schacher
Beate
B
Puklo
Magda
M
Eickholz
Peter
P
Hoffmann
Thomas
T
Schackert
Hans Konrad
HK
D000328:Adult; D010520:Aggressive Periodontitis / Q000201:enzymology* / Q000235:genetics*; D020789:Cathepsin C / Q000235:genetics*; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics; D020125:Mutation, Missense; D010214:Papillon-Lefevre Disease / Q000201:enzymology* / Q000235:genetics*; D010641:Phenotype
D018389:Codon, Nonsense; D020789:Cathepsin C; D019272:Leukocyte Elastase