LOCALIZATION OF A GENE FOR PAPILLON-LEFEVRE-SYNDROME TO CHROMOSOME 11Q14-Q21 BY HOMOZYGOSITY MAPPING

Papillon-Lefevre syndrome is an autosomal recessively inherited palmop lantar keratoderma of unknown aetiology associated with severe periodo ntitis leading to premature loss of dentition. Three consanguineous fa milies, two of Turkish and one of German origin, and three multiplex f amilies, one of Ethiopian and two of German origin, with 11 affected a nd 6 unaffected siblings in all were studied. A targeted genome search was initially attempted to several candidate gene regions but failed to demonstrate linkage. Therefore a genome-wide linkage scan using a c ombination of homozygosity mapping and traditional linkage analysis wa s undertaken. Linkage was obtained with marker D11S937 with a maximum two-point lod score of Z(max) = 6.1 at recombination fraction theta = 0.00 on chromosome 11q14-Pq21 near the metalloproteinase gene cluster. Multipoint likelihood calculations gave a maximum lod score of 7.35 b etween D11S901 and D11S1358. A 9.2-cM region homozygous by descent in the affected members of the three consanguineous families lies between markers D11S1989 and D11S4176 harbouring the as yet unknown Papillon- Lefevre syndrome gene. Haplotype analyses in all the families studied support this localisation. This study has identified a further locus h arbouring a gene for palmoplantar keratoderma and one possibly involve d in periodontitis.