Mutation analysis of the cathepsin C gene in Indian families with Papillon-Lefèvre syndrome

Selvaraju, Veeriah; Markandaya, Manjunath; Prasad, P. V. S.; Sathyan, Parthasarathy; Sethuraman, Gomathy; Srivastava, S. C.; Thakker, Nalin; Kumar, Arun

doi:10.1186/1471-2350-4-5

Cited by 49 publications

(66 citation statements)

References 22 publications

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“…However, such a correlation was not found. A similar result was found recently by Selvaraju et al (2003). In the present report, both patients of family 1 displayed a mild hyperkeratosis.…”

Section: Figuresupporting

confidence: 92%

Loss-of-function mutations in cathepsin C in two families with Papillon-Lefèvre syndrome are associated with deficiency of serine proteinases in PMNs

et al. 2004

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Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disease that involves severe periodontitis and hyperkeratosis of the hand palms and foot soles. Recently it was found that PLS patients carry loss-of-function mutations in the gene encoding cathepsin C (CTSC). In the present study we have analyzed the CTSC gene in two unrelated families with PLS. In the first non-consanguineous family, mutation analysis revealed the previously reported c.815G>C/p.R272P mutation. The second consanguineous family displayed a c.1213C>A mutation which resulted in the novel mutation p.H405N and is the first mutation described in the active site of the enzyme. The PLS patients had, next to the absence of cathepsin C activity in polymorphonuclear leukocytes (PMNs), no activity of the three serine proteinases elastase, cathepsin G and proteinase 3. Serine proteinases are supposed to be important in both the innate and adaptive immune systems. Their absence in PLS patients could explain the inadequate defense to periodontal infection.

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“…However, such a correlation was not found. A similar result was found recently by Selvaraju et al (2003). In the present report, both patients of family 1 displayed a mild hyperkeratosis.…”

Section: Figuresupporting

confidence: 92%

Loss-of-function mutations in cathepsin C in two families with Papillon-Lefèvre syndrome are associated with deficiency of serine proteinases in PMNs

et al. 2004

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“…Cathepsin C deficiency in humans causes PLS (Hart et al, 1999;Toomes et al, 1999). More than 41 mutations in the human cathepsin C gene have been documented (Selvaraju et al, 2003) and most patients with PLS tested exhibit an almost complete (Ͼ95%) loss of cathepsin C activity (de Haar et al, 2004;Hewitt et al, 2004;Pham et al, 2004;Nitta et al, 2005). In two published cases, relatives of PLS showed reduced cathepsin C activity but were asymptomatic (Hewitt et al, 2003;Nitta et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Inhibition of Serine Protease Processing Requires a High Fractional Inhibition of Cathepsin C

Méthot

Guay²,

Rubin³

et al. 2008

Mol Pharmacol

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Inhibition of cathepsin C, a dipeptidyl peptidase that activates many serine proteases, represents an attractive therapeutic strategy for inflammatory diseases with a high neutrophil burden. We recently showed the feasibility of blocking the activation of neutrophil elastase, cathepsin G, and proteinase-3 with a single cathepsin C selective inhibitor in cultured cells. Here we measured the fractional inhibition of cathepsin C that is required for blockade of downstream serine protease processing, in cell-based assays and in vivo. Using a radiolabeled active site probe and U937 cells, a 50% reduction of cathepsin G processing required ϳ50% of cathepsin C active sites to be occupied by an inhibitor. In EcoM-G cells, inhibition of 50% of neutrophil elastase activity required ϳ80% occupancy. Both of these serine proteases were fully inhibited at full cathepsin C active site occupancy, whereas granzyme B processing in TALL-104 cells was partially inhibited, despite complete occupancy. In vivo, leukocytes from cathepsin C ϩ/Ϫ mice exhibited comparable levels of neutrophil elastase activity to wild-type animals, even though their cathepsin C activity was reduced by half. The long-term administration of a cathepsin C inhibitor to rats, at doses that resulted in the nearly complete blockade of cathepsin C active sites in bone marrow, caused significant reductions of neutrophil elastase, cathepsin G and proteinase-3 activities. Our results demonstrate that the inhibition of cathepsin C leads to a decrease of activity of multiple serine proteases involved in inflammation but also suggest that high fractional inhibition is necessary to reach therapeutically significant effects.

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“…Le gène responsable du SPL qui a été localisé en 11q14/q21, code pour la cathepsine C. Le SPL résulte d'une mutation du gène codant pour cette protéine donnant une suppression totale de son activité [8] . Cette protéine joue un rôle essentiel dans l'établisse-ment et le maintien de l'organisation structurale de l'épithélium des extrémités (paumes, plantes), de même que dans l'intégrité des propriétés immunologiques des tissus de soutien des dents [8,11] . Concernant le cas présenté dans ce travail et après avis du généticien et du dermatologue, les signes cliniques et dermatologiques sont tellement évocateurs du syndrome que l'étude génétique n'a pas été réalisée.…”

Section: Discussionunclassified

Syndrome de Papillon-Lefèvre : à propos d’un cas

Alloussi

Bennazza²,

Rahmani³

et al. 2009

Med Buccale Chir Buccale

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RÉSUMÉCe cas concerne une jeune fille âgée de 3 ans qui présente un syndrome de Papillon-Lefèvre et dont le diagnostic est basé sur les données cliniques. Elle présentait des hyperkératoses plantaires dès la première consultation avec une parodontite sévère et des dents mobiles ; les lésions palmaires ne sont apparues que quelques mois après la première consultation. Le traitement initial a comporté la réalisation d'un traitement parodontal avec extractions des dents non conservables, puis la réalisation d'une prothèse dentaire pédiatrique.

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Mutation analysis of the cathepsin C gene in Indian families with Papillon-Lefèvre syndrome

Cited by 49 publications

References 22 publications

Loss-of-function mutations in cathepsin C in two families with Papillon-Lefèvre syndrome are associated with deficiency of serine proteinases in PMNs

Loss-of-function mutations in cathepsin C in two families with Papillon-Lefèvre syndrome are associated with deficiency of serine proteinases in PMNs

In Vivo Inhibition of Serine Protease Processing Requires a High Fractional Inhibition of Cathepsin C

Syndrome de Papillon-Lefèvre : à propos d’un cas

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