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

Abstract

Background: 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.

Methods: 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.

Results: We identified an identical recurrent missense mutation, R272P, in all 3 families. Microsatellite marker analysis around the CTSC gene revealed the same haplotype on the mutation-carrying allele in all 3 families.

Conclusion: The presence of this common mutation in families from 2 different geographical areas provides evidence for a founder effect for CTSC mutations in PLS.

Fig. 1.

Affected individuals showing palmoplantar hyperkeratosis (a, b) with progredient (c) and transgredient (d) spread. Psoriasiform lesions were present over the elbows (e) and knees (f). g A 12-year-old girl at the start of the second cycle of tooth involvement presenting with gingivitis and periodontitis. h A man in his fourth decade with nearly complete loss of his teeth.

Fig. 2.

Pedigrees from the 3 families reveal an autosomal recessive pattern of inheritance. Two families are from Pakistan (a, b) and one from Lebanon (c). d Affected individuals from the 3 families showing a homozygous mutation with a G→C change at nucleotide 815 (indicated by arrow), carriers being heterozygotes for the mutation; a control sequence is shown for comparison. Filled circles and squares represent females and males, respectively. Double lines indicate consanguinity.

Fig. 2.

Pedigrees from the 3 families reveal an autosomal recessive pattern of inheritance. Two families are from Pakistan (a, b) and one from Lebanon (c). d Affected individuals from the 3 families showing a homozygous mutation with a G→C change at nucleotide 815 (indicated by arrow), carriers being heterozygotes for the mutation; a control sequence is shown for comparison. Filled circles and squares represent females and males, respectively. Double lines indicate consanguinity.