Sublocalization of the Papillon-Lefevre syndrome locus on 11q14-q21

Abstract

Papillon-Lefevre syndrome (PLS) is an autosomal recessive form of palmoplantar ectodermal dysplasia, characterized by palmoplantar hyperkeratosis and severe early-onset periodontitis. The presence of severe periodontitis distinguishes PLS from other palmoplantar keratodermas. As part of our efforts to study the genetic basis of periodontitis susceptibility, we performed a genome-wide search to identify major loci for PLS in 44 individuals (14 affected) from 10 consanguineous PLS families. We have identified evidence for linkage of a PLS gene on 11q14-q21. A maximum two-point logarithm of the odds (LOD) score of 8.24 was obtained for D11S1367 at a recombination fraction of theta=0.00. Multipoint analysis resulted in a LOD score of 10.45 and placed the gene for PLS within a 4-5 cM genetic interval. This genetic interval, flanked by D11S4197 and D11S931, contains more than 50 cDNAs and 200 expressed sequence tags (ESTs). This refinement of the candidate region for a PLS gene is in agreement with other recent reports of linkage for PLS to chromosome 11q14-q21 and should help in identification of the gene for PLS.

The Impact of Molecular Genetics on Oral Health Paradigms

“…Three independent groups (Fischer et al, 1997;Laass et al, 1997;Hart et al, 1998b) Several examples of complex conditions of importance to the dental community include oral clefting, adult periodontitis, oral squamous cell carcinoma, and dental caries. Identification of the molecular targets of environmental agents will help us understand the disease process and develop appropriate treatment strategies.…”

Cathepsin C gene: First compound heterozygous patient with Papillon‐Lefèvre syndrome and a novel symptomless mutation

“…These proteases are implicated in a wide variety of innate and adaptive immune processes, which might explain a general increased susceptibility to infections in about 25% of PLS patients (Góngora et al, 1994). The PLS locus has been mapped to chromosome 11q14-q21 band (Fischer et al, 1997;Laass et al, 1997;Hart et al, 1998); CTSC gene spans 4.7 kb and encodes a 463-amino acid polypeptide that consists of 7 exons. The sequence analysis of CTSC gene from subjects that belong to consanguineous families and were affected with PLS and HMS revealed homozygous sequence changes in all the patients (Toomes et al, 1999;Hart et al, 1999Hart et al, , 2000aHart et al, , 2000b.…”

Pyogenic Liver Abscess and Papillon-Lefèvre Syndrome: Not a Rare Association

“…31,32 In 1999, Hart et al 33 identified a germline missense and truncating mutations in the gene encoding cathepsin C (or dipeptidyl aminopeptidase I), a lysosomal cysteine proteinase that plays an important role in intracellular degradation of proteins in families with PLS. Cathepsin C is an enzyme that processes and activates several granule serine proteases critical to immune and inflammatory responses of myeloid and lymphoid cells.…”