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J Med Genet. Feb 2001; 38(2): 96–101.
PMCID: PMC1734811

Evidence of a founder effect for four cathepsin C gene mutations in Papillon-Lefèvre syndrome patients


We describe a mutation and haplotype analysis of Papillon-Lefèvre syndrome probands that provides evidence of a founder effect for four separate cathepsin C mutations. A total of 25 different cathepsin C mutations have been reported in 32 families with Papillon-Lefèvre syndrome (PLS) and associated conditions. A characteristic of these findings is the diversity of different cathepsin C mutations that have been identified. To evaluate the generality of cathepsin C mutations, PLS probands representative of five reportedly unrelated Saudi Arabian families were evaluated by mutational and haplotype analyses. Sequence analysis identified two cathepsin C gene mutations: a novel exon 7 G300D mutation was found in the proband from one family, while probands from four families shared a common R272P mutation in exon 6. The R272P mutation has been previously reported in two other non-Saudi families. The presence of the R272P mutation in probands from these four Saudi families makes this the most frequently reported cathepsin C mutation. To distinguish between the presence of a possible founder effect or a mutational hot spot for the R272P mutation, we performed haplotype analysis using six novel DNA polymorphisms that span a 165 kb interval containing the cathepsin C gene. Results of haplotype analysis for genetic polymorphisms within and flanking the cathepsin C gene are consistent with inheritance of the R272P mutation "identical by descent" from a common ancestor in these four Saudi families. Haplotype analysis of multiple PLS probands homozygous for other cathepsin C mutations (W249X, Q286X, and T153I) also supports inheritance of each of these mutations from common ancestors. These data suggest that four of the more frequently reported cathepsin C mutations have been inherited from common ancestors and provide the first direct evidence for a founder effect for cathepsin C gene mutations in PLS. Identification of these six short tandem repeat polymorphisms that span the cathepsin C gene will permit haplotype analyses to determine other founder haplotypes of cathepsin C mutations in additional PLS families.

Keywords: Papillon-Lefèvre syndrome; cathepsin C; founder effect; chromosome 11q14

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Selected References

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  • Stevens HP, Kelsell DP, Bryant SP, Bishop DT, Spurr NK, Weissenbach J, Marger D, Marger RS, Leigh IM. Linkage of an American pedigree with palmoplantar keratoderma and malignancy (palmoplantar ectodermal dysplasia type III) to 17q24. Literature survey and proposed updated classification of the keratodermas. Arch Dermatol. 1996 Jun;132(6):640–651. [PubMed]
  • Haneke E. The Papillon-Lefèvre syndrome: keratosis palmoplantaris with periodontopathy. Report of a case and review of the cases in the literature. Hum Genet. 1979 Sep 2;51(1):1–35. [PubMed]
  • Hart TC, Hart PS, Bowden DW, Michalec MD, Callison SA, Walker SJ, Zhang Y, Firatli E. Mutations of the cathepsin C gene are responsible for Papillon-Lefèvre syndrome. J Med Genet. 1999 Dec;36(12):881–887. [PMC free article] [PubMed]
  • Toomes C, James J, Wood AJ, Wu CL, McCormick D, Lench N, Hewitt C, Moynihan L, Roberts E, Woods CG, et al. Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis. Nat Genet. 1999 Dec;23(4):421–424. [PubMed]
  • Hart PS, Zhang Y, Firatli E, Uygur C, Lotfazar M, Michalec MD, Marks JJ, Lu X, Coates BJ, Seow WK, et al. Identification of cathepsin C mutations in ethnically diverse papillon-Lefèvre syndrome patients. J Med Genet. 2000 Dec;37(12):927–932. [PMC free article] [PubMed]
  • Pareek SS, Al-Aska AK. Papillon-Lefevre syndrome. A report of six cases in one family. Int J Dermatol. 1986 Dec;25(10):638–641. [PubMed]
  • Adbulwassie H, Dhanrajani PJ, Jiffry A. Papillon-Lefèvre syndrome. Reappraisal of etiology, clinical features and treatment. II. Oral rehabilitation using osseointegrated implants. Indian J Dent Res. 1996 Apr-Jun;7(2):63–70. [PubMed]
  • Lundgren T, Twetman S, Johansson I, Crossner CG, Birkhed D. Saliva composition in children and young adults with Papillon-Lefèvre syndrome. J Clin Periodontol. 1996 Dec;23(12):1068–1072. [PubMed]
  • Lundgren T, Crossner CG, Twetman S, Ullbro C. Systemic retinoid medication and periodontal health in patients with Papillon-Lefèvre syndrome. J Clin Periodontol. 1996 Mar;23(3 Pt 1):176–179. [PubMed]
  • Lundgren T, Renvert S, Papapanou PN, Dahlén G. Subgingival microbial profile of Papillon-Lefèvre patients assessed by DNA-probes. J Clin Periodontol. 1998 Aug;25(8):624–629. [PubMed]
  • Zhang J, Madden TL. PowerBLAST: a new network BLAST application for interactive or automated sequence analysis and annotation. Genome Res. 1997 Jun;7(6):649–656. [PMC free article] [PubMed]
  • Fischer J, Blanchet-Bardon C, Prud'homme JF, Pavek S, Steijlen PM, Dubertret L, Weissenbach J. Mapping of Papillon-Lefevre syndrome to the chromosome 11q14 region. Eur J Hum Genet. 1997 May-Jun;5(3):156–160. [PubMed]
  • Laass MW, Hennies HC, Preis S, Stevens HP, Jung M, Leigh IM, Wienker TF, Reis A. Localisation of a gene for Papillon-Lefèvre syndrome to chromosome 11q14-q21 by homozygosity mapping. Hum Genet. 1997 Dec;101(3):376–382. [PubMed]
  • Hart TC, Bowden DW, Ghaffar KA, Wang W, Cutler CW, Cebeci I, Efeoglu A, Firatli E. Sublocalization of the Papillon-Lefevre syndrome locus on 11q14-q21. Am J Med Genet. 1998 Sep 1;79(2):134–139. [PubMed]
  • Hart TC, Walker SJ, Bowden DW, Hart PS, Callison SA, Bobby PL, Firatli E. An integrated physical and genetic map of the PLS locus interval on chromosome 11q14. Mamm Genome. 2000 Mar;11(3):243–246. [PubMed]
  • Benson G. Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res. 1999 Jan 15;27(2):573–580. [PMC free article] [PubMed]
  • Deloukas P, Schuler GD, Gyapay G, Beasley EM, Soderlund C, Rodriguez-Tomé P, Hui L, Matise TC, McKusick KB, Beckmann JS, et al. A physical map of 30,000 human genes. Science. 1998 Oct 23;282(5389):744–746. [PubMed]

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