One mutation, two phenotypes: a single nonsense mutation of the<i>CTSC</i>gene causes two clinically distinct phenotypes

Sulák, Adrienn; Tóth, László; Farkas, Katalin; Tripolszki, Kornélia; Fábos, Beáta; Kemény, Lajos; Vályi, Péter; Nagy, Katalin; Nagy, Nikoletta; Széll, Márta

doi:10.1111/ced.12710

Cited by 13 publications

(22 citation statements)

References 26 publications

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“…Also known as Papillon‐Lefévre syndrome, PPK with periodontitis is an autosomal recessive disorder characterized by PPK, periodontitis, and premature loss of dentition. Although apparently clinically distinct, Papillion‐Lefévre and Haim‐Munk syndromes represent varying degrees of severity of the same disorder, and may both result from the same CTSC mutation . Cathepsin C, or dipeptidyl aminopeptidase, is a lysosomal protease that removes dipeptides from the amino terminus of protein substrates, thus processing a variety of serine proteases considered essential for antimicrobial defense.…”

Section: Syndromic Palmoplantar Keratodermasmentioning

confidence: 99%

Palmoplantar keratodermas: clinical and genetic aspects

Has

Technau‐Hafsi

2016

J Deutsche Derma Gesell

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Summary Palmoplantar keratodermas comprise a diverse group of acquired and hereditary disorders marked by excessive thickening of the epidermis of palms and soles. Early onset and positive family history suggest a genetic cause. While hereditary forms of palmoplantar keratoderma (PPK) may represent the sole or dominant clinical feature, they may also be associated with other ectodermal defects or extracutaneous manifestations. In recent years, much progress has been made in deciphering the genetic basis of PPK, which has led to the emergence of new disorders and syndromes. The elucidation of disease mechanisms has opened new avenues for specific therapies, increasingly sparking interest in this field. Given the high heterogeneity with respect to clinical features, genetic defects, and disease mechanisms, the classification of PPK is based on various criteria. These include extent of disease manifestations, morphology of palmoplantar skin involvement, inheritance patterns, and molecular pathogenesis. Though not always feasible, the clinical distinction of various PPK entities is based on fine‐tuned criteria or clues. Remarkably, apparently distinct disorders have been shown to be allelic, as they are caused by mutations in the same gene. By contrast, similar clinical pictures may result from mutations in different genes. Because of this complexity, mutation analysis is required to determine the precise type of PPK. The best‐defined entities are described in this review.

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Section: Syndromic Palmoplantar Keratodermasmentioning

confidence: 99%

Palmoplantar keratodermas: clinical and genetic aspects

Has

Technau‐Hafsi

2016

J Deutsche Derma Gesell

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“…Papillon-Lef evre syndrome (PLS)-Pathogenesis-PLS, a very rare AR disorder discovered in 1924, is characterized by palmoplantar hyperkeratosis (PPK) and severe periodontitis (Van Dyke et al, 1984;Dalgic et al, 2011). Haim-Munk syndrome (HMS) is a phenotypic variant of PLS (Sulak et al, 2016). The presence of early aggressive periodontal disease is what distinguishes PLS and HMS from more common forms of PPK (Hart et al, 1997).…”

Section: Oral Diseasesmentioning

confidence: 99%

Periodontal and other oral manifestations of immunodeficiency diseases

2016

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The list of immunodeficiency diseases grows each year as novel disorders are discovered, classified, and sometimes reclassified due to our ever-increasing knowledge of immune system function. Although the number of patients with secondary immunodeficiencies (SIDs) greatly exceeds those with primary immunodeficiencies (PIDs), the prevalence of both appears to be on the rise probably because of scientific breakthroughs that facilitate earlier and more accurate diagnosis. Primary immunodeficiencies in adults are not as rare as once thought. Globally, the main causes of secondary immunodeficiency are HIV infection and nutritional insufficiencies. Persons with acquired immune disorders such as AIDS caused by the Human Immunodeficiency Virus (HIV) are now living long and fulfilling lives as a result of highly active antiretroviral therapy (HAART). Irrespective of whether the patient’s immune deficient state is a consequence of a genetic defect or is secondary in nature, dental and medical practitioners must be aware of the constant potential for infections and/or expressions of autoimmunity in these individuals. The purpose of this paper is to review the most common conditions resulting from primary and secondary immunodeficiency states, how they are classified, and the detrimental manifestations of these disorders on the periodontal and oral tissues.

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“…It is secreted by activated neutrophils as confirmed through lipopolysaccharide (LPS) administration in a non-human primate model (Hamon et al, 2016). In cathepsin C-deficient mice, the function of the cytotoxic T cells is impaired (Pham and Ley, 1999) whereas in humans, defects in the cathepsin C gene are associated with Papillon-Lefevre disease, Haim-Munk syndrome (Sulák et al, 2016) and aggressive periodontitis (Nagy et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

Salivary Tick Cystatin OmC2 Targets Lysosomal Cathepsins S and C in Human Dendritic Cells

Zavašnik–Bergant

Vidmar

Sekirnik

et al. 2017

Front. Cell. Infect. Microbiol.

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To ensure successful feeding tick saliva contains a number of inhibitory proteins that interfere with the host immune response and help to create a permissive environment for pathogen transmission. Among the potential targets of the salivary cystatins are two host cysteine proteases, cathepsin S, which is essential for antigen- and invariant chain-processing, and cathepsin C (dipeptidyl peptidase 1, DPP1), which plays a critical role in processing and activation of the granule serine proteases. Here, the effect of salivary cystatin OmC2 from Ornithodoros moubata was studied using differentiated MUTZ-3 cells as a model of immature dendritic cells of the host skin. Following internalization, cystatin OmC2 was initially found to inhibit the activity of several cysteine cathepsins, as indicated by the decreased rates of degradation of fluorogenic peptide substrates. To identify targets, affinity chromatography was used to isolate His-tagged cystatin OmC2 together with the bound proteins from MUTZ-3 cells. Cathepsins S and C were identified in these complexes by mass spectrometry and confirmed by immunoblotting. Furthermore, reduced increase in the surface expression of MHC II and CD86, which are associated with the maturation of dendritic cells, was observed. In contrast, human inhibitor cystatin C, which is normally expressed and secreted by dendritic cells, did not affect the expression of CD86. It is proposed that internalization of salivary cystatin OmC2 by the host dendritic cells targets cathepsins S and C, thereby affecting their maturation.

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One mutation, two phenotypes: a single nonsense mutation of theCTSCgene causes two clinically distinct phenotypes

Cited by 13 publications

References 26 publications

Palmoplantar keratodermas: clinical and genetic aspects

Palmoplantar keratodermas: clinical and genetic aspects

Periodontal and other oral manifestations of immunodeficiency diseases

Salivary Tick Cystatin OmC2 Targets Lysosomal Cathepsins S and C in Human Dendritic Cells

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