Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation
- T C Harta,
- P S Hartb,
- M D Michalecb,
- Y Zhanga,
- M L Marazitab,c,
- M Cooperc,
- O M Yassind,
- M Nusiere,
- S Walkerf
- aDepartment of Oral Medicine/Pathology, University of Pittsburgh, School of Dental Medicine, 614 Salk Hall, 3501 Terrace Street, Pittsburgh, PA 15261, USA, bDepartment of Human Genetics, University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA 15261, USA, cCleft Palate- Craniofacial Center, University of Pittsburgh, School of Dental Medicine, Pittsburgh, PA 15261, USA, dDepartment of Paediatric Dentistry, Al-Amir Rashid Hospital, Royal Medical Services, Jordan, eDepartment of Biochemistry and Molecular Biology, Jordan University of Science and Technology, School of Medicine, Irbid, Jordan, fDepartment of Pediatrics, Wake Forest University, School of Medicine, Winston Salem, NC 27157, USA
- Dr T C Hart
- Revised 3 December 1999
- Accepted 4 December 1999
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.
