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

Allende, Luís M.; Garcı́a-Pérez, Miguel A.; Moreno, Ángel; Corell, Alfredo; Carasol, Miguel; Martinez-Canut, Pedro; Arnaiz‐Villena, Antonio

doi:10.1002/1098-1004(200102)17:2<152::aid-humu10>3.0.co;2-#

Cited by 31 publications

(31 citation statements)

References 12 publications

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“…2002; [16] Nakano et al 2001; [15] Hart et al 2000c; [17] Zhang et al 2001; [18] Allende et al 2001; [19] Lefevre et al 2001; [7]Toomes et al 1999; [3] Cury et al 2002; [21] Hart et al 2002; [10] Hart et al 2000b; [14] Hart et al 1999; [22] Nusier et al 2002; [9] Hart et al 2000a. * Proband was a compound heterozygote for the 199–222 del and 458C>T mutations ** Alteration of highly conserved residue.…”

Section: Discussionmentioning

confidence: 99%

“…A missense mutation c.857A>G (p.Q286R) in the CTSC gene has been found to cause HMS [9]. This mutation has also been detected in a homozygous state in a Spanish PLS patient, suggesting that the HMS and PLS are clinical variants of the same homozygous cathepsin C gene mutation [18]. It is possible that a part of the clinical manifestations in HMS patients (viz., hyperkeratosis and periodontitis) is caused by a mutation in the CTSC gene where as other features of HMS (viz., onychogryposis, pes planus, arachnodactyly, and acroosteolysis) are caused by mutations in another hitherto undescribed gene.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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Background: PLS is a rare autosomal recessive disorder characterized by early onset periodontopathia and palmar plantar keratosis. PLS is caused by mutations in the cathepsin C (CTSC) gene. Dipeptidyl-peptidase I encoded by the CTSC gene removes dipeptides from the aminoterminus of protein substrates and mainly plays an immune and inflammatory role. Several mutations have been reported in this gene in patients from several ethnic groups. We report here mutation analysis of the CTSC gene in three Indian families with PLS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2003

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“…Five compound heterozygous mutations of the CTSC gene in Papillon-Lefèvre syndrome have been reported in other ethnic groups (Hart et al, 2000;Allende et al, 2001;Zhang et al, 2002;Noack et al, 2004).…”

Section: Discussionmentioning

confidence: 98%

Novel Mutations of Cathepsin C Gene in Two Chinese Patients with Papillon-Lefèvre Syndrome

et al. 2007

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Papillon-Lefèvre syndrome (PLS) is an inherited human disease characterized by early-onset periodontitis and palmoplantar hyperkeratosis. Mutations of the lysosomal protease cathepsin C (CTSC) gene have been shown to be the genetic cause of Papillon-Lefèvre syndrome. There are several case reports in China, while there has been no study on the genetic analysis of PLS. We studied two Chinese patients carrying Papillon-Lefèvre syndrome and showing premature tooth loss and palmoplantar hyperkeratosis. Mutation screening and sequence analysis of the CTSC gene revealed a compound heterozygous mutation (c.415 G>A and c.778 T>C) in one patient, and two novel compound heterozygous mutations (c.851G>A and c.112delCCTG) in the other patient. Our novel discovery indicates that the phenotypes observed in these two patients are due to the CTSC gene mutation.

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“…Additionally, identical mutations have been found in PLS and in the closely related Haim-Munk syndrome [46][47][48]. The p.G301S and the p.R272P mutation, which was discovered in typical PLS families [12-14, 17, 26, 44, 49, 50], have been also associated with atypical cases, late onset of periodontitis [45] and mild skin lesions [16]. A seven base-pair deletion (p.T189FS199X) in one prepubertal periodontitis family [27] was also found in two of the analyzed typical PLS families and has been reported previously in PLS [26].…”

Section: Discussionmentioning

confidence: 99%

“…Another source of variance may be the different mutations of the CTSC gene itself. Atypical PLS cases have been described exhibiting CTSC gene mutations [14,33,[41][42][43][44][45]. These cases included mild or missing skin findings as well as later onset of periodontitis or mild periodontal destruction.…”

Section: Discussionmentioning

confidence: 99%

Cytokine production by leukocytes of Papillon–Lefèvre syndrome patients in whole blood cultures

et al. 2011

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Papillon-Lefèvre syndrome (PLS) is characterised by aggressively progressive periodontitis combined with palmo-plantar hyperkeratosis. It is caused by "loss of function" mutations in the cathepsin C gene. The hypothesis behind this study is that PLS patients' polymorphonuclear leukocytes (PMNs) produce more proinflammatory cytokines to compensate for their reduced capacity to neutralize leukotoxin and to eliminate Aggregatibacter actinomycetemcomitans. Production of more interleukin (IL)-8 would result in the attraction of more PMNs. The aim of this study was to evaluate the cytokine profile in PLS patients' blood cultures. Blood was sampled from eight PLS patients (one female) from six families (antiinfective therapy completed: six; edentulous: two) with confirmed cathepsin C mutations and deficient enzyme activity. Nine healthy males served as controls. Whole blood cultures were stimulated with highly pure lipopolysaccharide (LPS) from Escherichia coli R515 and IL-1β plus tumor necrosis factor (TNF)-α. Thereafter, release of IL-1β (stimulation: LPS and LPS plus adenosine triphosphate), IL-6, IL-8, interferon-inducible protein (IP)-10, and interferon (IFN)-γ (stimulation: LPS, IL-1β/TNFα) were detected by ELISA. Medians of cytokine release were, with the exception of IP-10, slightly higher for PLS than for controls' cultures. None of these differences reached statistical significance. Increased production of IL-1β, IL-6, IL-8, IP-10, or IFNγ as a significant means to compensate for diminished activity and stability of polymorphonuclear leukocyte-derived proteases could not be confirmed in this study. Cytokine profiles in blood cultures may not be used to identify PLS patients.

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

Cited by 31 publications

References 12 publications

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

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

Novel Mutations of Cathepsin C Gene in Two Chinese Patients with Papillon-Lefèvre Syndrome

Cytokine production by leukocytes of Papillon–Lefèvre syndrome patients in whole blood cultures

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