Evidence for a founder mutation in the cathepsin C gene in three families with Papillon-Lefèvre syndrome.

[papillon-lefèvre syndrome]

Papillon-Lefèvre syndrome (PLS ; OMIM 245000 ) is a rare autosomal recessive disorder . Clinically , PLS is characterized by hyperkeratosis involving the palms , soles , elbows and knees which is followed later on by periodontitis , destruction of alveolar bone and loss of primary and permanent teeth . The condition is caused by mutations in the cathepsin C (CTSC ) gene .We analyzed the DNA of members from 3 consanguineous families for mutations in the CTSC gene by direct sequencing analysis . We then performed haplotype analysis .We identified an identical recurrent missense mutation , R 272 P , in all 3 families . Microsatellite marker analysis around the CTSC gene revealed the same haplotype on the mutation -carrying allele in all 3 families .The presence of this common mutation in families from 2 different geographical areas provides evidence for a founder effect for CTSC mutations in PLS .