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J Med Genet. Feb 2000; 37(2): 95–101.
PMCID: PMC1734516

Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation

Abstract

Prepubertal periodontitis (PPP) is a rare and rapidly progressive disease of young children that results in destruction of the periodontal support of the primary dentition. The condition may occur as part of a recognised syndrome or may occur as an isolated finding. Both autosomal dominant and recessive forms of Mendelian transmission have been reported for PPP. We report a consanguineous Jordanian family with four members affected by PPP in two nuclear sibships. The parents of the affected subjects are first cousins. We have localised a gene of major effect for PPP in this kindred (Zmax=3.55 for D11S901 at θ=0.00) to a 14 cM genetic interval on chromosome 11q14 flanked by D11S916 and D11S1367. This PPP candidate interval overlaps the region of chromosome 11q14 that contains the cathepsin C gene responsible for Papillon-Lefèvre and Haim-Munk syndromes. Sequence analysis of the cathepsin C gene from PPP affected subjects from this Jordanian family indicated that all were homozygous for a missense mutation (1040A→G) that changes a tyrosine to a cysteine. All four parents were heterozygous carriers of this Tyr347Cys cathepsin C mutation. None of the family members who were heterozygous carriers for this mutation showed any clinical findings of PPP. None of the 50 controls tested were found to have this Tyr347Cys mutation. This is the first reported gene mutation for non-syndromic periodontitis and shows that non-syndromic PPP is an allelic variant of the type IV palmoplantar ectodermal dysplasias.


Keywords: prepubertal periodontitis; periodontal disease; cathepsin C; linkage

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Selected References

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  • Page RC, Bowen T, Altman L, Vandesteen E, Ochs H, Mackenzie P, Osterberg S, Engel LD, Williams BL. Prepubertal periodontitis. I. Definition of a clinical disease entity. J Periodontol. 1983 May;54(5):257–271. [PubMed]
  • Watanabe K. Prepubertal periodontitis: a review of diagnostic criteria, pathogenesis, and differential diagnosis. J Periodontal Res. 1990 Jan;25(1):31–48. [PubMed]
  • López NJ. Clinical, laboratory, and immunological studies of a family with a high prevalence of generalized prepubertal and juvenile periodontitis. J Periodontol. 1992 May;63(5):457–468. [PubMed]
  • Shapira L, Schlesinger M, Bimstein E. Possible autosomal-dominant inheritance of prepubertal periodontitis in an extended kindred. J Clin Periodontol. 1997 Jun;24(6):388–393. [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, 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]
  • GORLIN RJ, SEDANO H, ANDERSON VE. THE SYNDROME OF PALMAR-PLANTAR HYPERKERATOSIS AND PREMATURE PERIODONTAL DESTRUCTION OF THE TEETH. A CLINICAL AND GENETIC ANALYSIS OF THE PAPILLON-LEF'EVRE SYNDROME. J Pediatr. 1964 Dec;65:895–908. [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]
  • 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]
  • Weissenbach J, Gyapay G, Dib C, Vignal A, Morissette J, Millasseau P, Vaysseix G, Lathrop M. A second-generation linkage map of the human genome. Nature. 1992 Oct 29;359(6398):794–801. [PubMed]
  • Dib C, Fauré S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E, et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. [PubMed]
  • O'Connell JR, Weeks DE. The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set-recoding and fuzzy inheritance. Nat Genet. 1995 Dec;11(4):402–408. [PubMed]
  • Davis S, Schroeder M, Goldin LR, Weeks DE. Nonparametric simulation-based statistics for detecting linkage in general pedigrees. Am J Hum Genet. 1996 Apr;58(4):867–880. [PMC free article] [PubMed]
  • Cleves MA, Olson JM, Jacobs KB. Exact transmission-disequilibrium tests with multiallelic markers. Genet Epidemiol. 1997;14(4):337–347. [PubMed]
  • Lander ES, Green P. Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2363–2367. [PMC free article] [PubMed]
  • Hart TC, Hart PS, Michalec MD, Zhang Y, Firatli E, Van Dyke TE, Stabholz A, Zlotogorski A, Shapira L, Soskolne WA, et al. Haim-Munk syndrome and Papillon-Lefèvre syndrome are allelic mutations in cathepsin C. J Med Genet. 2000 Feb;37(2):88–94. [PMC free article] [PubMed]
  • Papapanou PN. Periodontal diseases: epidemiology. Ann Periodontol. 1996 Nov;1(1):1–36. [PubMed]
  • Armitage GC. Periodontal diseases: diagnosis. Ann Periodontol. 1996 Nov;1(1):37–215. [PubMed]
  • Offenbacher S. Periodontal diseases: pathogenesis. Ann Periodontol. 1996 Nov;1(1):821–878. [PubMed]
  • Hart TC, Kornman KS. Genetic factors in the pathogenesis of periodontitis. Periodontol 2000. 1997 Jun;14:202–215. [PubMed]
  • Marazita ML, Burmeister JA, Gunsolley JC, Koertge TE, Lake K, Schenkein HA. Evidence for autosomal dominant inheritance and race-specific heterogeneity in early-onset periodontitis. J Periodontol. 1994 Jun;65(6):623–630. [PubMed]
  • Boughman JA, Halloran SL, Roulston D, Schwartz S, Suzuki JB, Weitkamp LR, Wenk RE, Wooten R, Cohen MM. An autosomal-dominant form of juvenile periodontitis: its localization to chromosome 4 and linkage to dentinogenesis imperfecta and Gc. J Craniofac Genet Dev Biol. 1986;6(4):341–350. [PubMed]
  • Hart TC, Marazita ML, McCanna KM, Schenkein HA, Diehl SR. Reevaluation of the chromosome 4q candidate region for early onset periodontitis. Hum Genet. 1993 Jun;91(5):416–422. [PubMed]
  • Nagle DL, Karim MA, Woolf EA, Holmgren L, Bork P, Misumi DJ, McGrail SH, Dussault BJ, Jr, Perou CM, Boissy RE, et al. Identification and mutation analysis of the complete gene for Chediak-Higashi syndrome. Nat Genet. 1996 Nov;14(3):307–311. [PubMed]
  • Marlin SD, Morton CC, Anderson DC, Springer TA. LFA-1 immunodeficiency disease. Definition of the genetic defect and chromosomal mapping of alpha and beta subunits of the lymphocyte function-associated antigen 1 (LFA-1) by complementation in hybrid cells. J Exp Med. 1986 Sep 1;164(3):855–867. [PMC free article] [PubMed]
  • Hogg N, Stewart MP, Scarth SL, Newton R, Shaw JM, Law SK, Klein N. A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1. J Clin Invest. 1999 Jan;103(1):97–106. [PMC free article] [PubMed]
  • Sturla L, Etzioni A, Bisso A, Zanardi D, De Flora G, Silengo L, De Flora A, Tonetti M. Defective intracellular activity of GDP-D-mannose-4,6-dehydratase in leukocyte adhesion deficiency type II syndrome. FEBS Lett. 1998 Jun 16;429(3):274–278. [PubMed]
  • Hartsfield JK, Jr, Kousseff BG. Phenotypic overlap of Ehlers-Danlos syndrome types IV and VIII. Am J Med Genet. 1990 Dec;37(4):465–470. [PubMed]
  • Rao NV, Rao GV, Hoidal JR. Human dipeptidyl-peptidase I. Gene characterization, localization, and expression. J Biol Chem. 1997 Apr 11;272(15):10260–10265. [PubMed]
  • Hola-Jamriska L, Tort JF, Dalton JP, Day SR, Fan J, Aaskov J, Brindley PJ. Cathepsin C from Schistosoma japonicum--cDNA encoding the preproenzyme and its phylogenetic relationships. Eur J Biochem. 1998 Aug 1;255(3):527–534. [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]
  • Passos-Bueno MR, Wilcox WR, Jabs EW, Sertié AL, Alonso LG, Kitoh H. Clinical spectrum of fibroblast growth factor receptor mutations. Hum Mutat. 1999;14(2):115–125. [PubMed]
  • Bullon P, Pascual A, Fernandez-Novoa MC, Borobio MV, Muniain MA, Camacho F. Late onset Papillon-Lefèvre syndrome? A chromosomic, neutrophil function and microbiological study. J Clin Periodontol. 1993 Oct;20(9):662–667. [PubMed]
  • Soskolne WA, Stabholz A, van Dyke TE, Hart TC, Meyle J. Partial expression of the Papillon-Lefèvre syndrome in 2 unrelated families. J Clin Periodontol. 1996 Aug;23(8):764–769. [PubMed]

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