The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis

We have previously reported that loss-of-function mutations in the cathepsin C gene (CTSC) result in Papillon Lefevre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early,onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non-mendelian, early-onset, severe periodontitis ("aggressive periodontitis") has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p. V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure-function relationships of CTSC. Our data also suggest that a complete loss-of-function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age-sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 +/- SD 576.8 mu moles/mg/min vs. 1,678.7 +/- SD 527.2 mu moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS. (C) 2004 Wiley-Liss, Inc.

Tracing Inspiration in Proverbial Material: From 'The Royal Dictionary' (1699 & 1729) of Abel Boyer to 'The English-Irish Dictionary' (1732) of Begley-McCurtin.

This metalexicographic study examines the relationship between the proverbial material in The English-Irish Dictionary (1732) of Begley and McCurtin, Abel Boyer’s The Royal Dictionary (First edition 1699, second edition 1729), and Nathaniel Bailey’s An Universal Etymological English Dictionary (1721). It will show, for the first time, that both the English macrostructure and microstructure of the proverbial entries in Begley and McCurtin (1732) were reproduced directly from Boyer’s dictionary and, in spite of claims to the contrary, the impact of Bailey’s (1721) dictionary was negligible. Furthermore, empirical data gleaned from a comparative linguistic analysis of the various editions of The Royal Dictionary prior to 1732, will prove that it was the second official edition (1729) that was used as the framework for The English-Irish Dictionary. A quantitative and qualitative analysis of the nature of the proverbial entries will also outline the various translation strategies that were used to compose the Irish material— particularly literal translation—and show that there are extremely high-levels of borrowings from Boyer (1729), both in terms of the English entries under the lemma, and the French entries in the comment.