Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients

Romero-Quintana, José Geovanni; Frías-Castro, Luis O; Arámbula-Meraz, Eliakym; Aguilar‐Medina, Maribel; Dueñas-Arias, Jesús E.; Melchor-Soto, Jesús D; Romero-Navarro, José G; Ramos‐Payán, Rosalío

doi:10.1186/1471-2350-14-7

Cited by 23 publications

(26 citation statements)

References 47 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NSPs themselves should act as useful biomarkers in understanding this effect. For example, it should be relatively straightforward to monitor the NSP activity and DPP1 inhibition in blood in early phase 1 clinical trials using established techniques (Stevens et al, 2011;Romero-Quintana et al, 2013). Such readily accessible biomarkers should enable good evidence of proof of mechanism to be achieved early in the development process for a suitable DPP1 inhibitor candidate drug.…”

Section: Figurementioning

confidence: 99%

Neutrophil maturation rate determines the effects of dipeptidyl peptidase 1 inhibition on neutrophil serine protease activity

Gardiner

Wikell

Clifton

et al. 2016

British J Pharmacology

View full text Add to dashboard Cite

Background and PurposeNeutrophil serine proteases (NSPs) are activated by dipeptidyl peptidase 1 (DPP1) during neutrophil maturation. The effects of neutrophil turnover rate on NSP activity following DPP1 inhibition was studied in a rat pharmacokinetic/pharmacodynamic model.Experimental ApproachRats were treated with a DPP1 inhibitor twice daily for up to 14 days; NSP activity was measured in onset or recovery studies, and an indirect response model was fitted to the data to estimate the turnover rate of the response.Key ResultsMaximum NSP inhibition was achieved after 8 days of treatment and a reduction of around 75% NSP activity was achieved at 75% in vitro DPP1 inhibition. Both the rate of inhibition and recovery of NSP activity were consistent with a neutrophil turnover rate of between 4–6 days. Using human neutrophil turnover rate, it is predicted that maximum NSP inhibition following DPP1 inhibition takes around 20 days in human.Conclusions and ImplicationsFollowing inhibition of DPP1 in the rat, the NSP activity was determined by the amount of DPP1 inhibition and the turnover of neutrophils and is thus supportive of the role of neutrophil maturation in the activation of NSPs. Clinical trials to monitor the effect of a DPP1 inhibitor on NSPs should take into account the delay in maximal response on the one hand as well as the potential delay in a return to baseline NSP levels following cessation of treatment.

show abstract

Section: Figurementioning

confidence: 99%

Neutrophil maturation rate determines the effects of dipeptidyl peptidase 1 inhibition on neutrophil serine protease activity

Gardiner

Wikell

Clifton

et al. 2016

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…; Romero‐Quintana et al. ). The c.1213delCAT p.His405del in‐frame deletion was reported in homozygous form in an Indian PLS patient (Wani et al.…”

Section: Other Deletionsmentioning

confidence: 99%

“…,b; Romero‐Quintana et al. ). Moreover, mild mental retardation, intracranial calcifications, and hyperhidrosis can also occur (Haneke ).…”

Section: Introductionmentioning

confidence: 96%

CTSC and Papillon–Lefèvre syndrome: detection of recurrent mutations in Hungarian patients, a review of published variants and database update

Nagy

Vályi

Csoma

et al. 2014

Molec Gen & Gen Med

View full text Add to dashboard Cite

Papillon–Lefèvre syndrome (PLS; OMIM 245000) is an autosomal recessive condition characterized by palmoplantar hyperkeratosis and periodontitis. In 1997, the gene locus for PLS was mapped to 11q14-21, and in 1999, variants in the cathepsin C gene (CTSC) were identified as causing PLS. To date, a total of 75 different disease-causing mutations have been published for the CTSC gene. A summary of recurrent mutations identified in Hungarian patients and a review of published mutations is presented in this update. Comparison of clinical features in affected families with the same mutation strongly confirm that identical mutations of the CTSC gene can give rise to multiple different phenotypes, making genotype–phenotype correlations difficult. Variable expression of the phenotype associated with the same CTSC mutation may reflect the influence of other genetic and/or environmental factors. Most mutations are missense (53%), nonsense (23%), or frameshift (17%); however, in-frame deletions, one splicing variant, and one 5′ untranslated region (UTR) mutation have also been reported. The majority of the mutations are located in exons 5–7, which encodes the heavy chain of the cathepsin C protein, suggesting that tetramerization is important for cathepsin C enzymatic activity. All the data reviewed here have been submitted to the CTSC base, a mutation registry for PLS at http://bioinf.uta.fi/CTSCbase/.

show abstract

“…Specific PPK forms can be recognized by prominent mucosal involvement. In particular, severe periodontitis with premature tooth decay typifies two peculiar PPKs due to mutations of the cathepsin C (CTSC) gene [21][22][23][24] (Table S1): the Haim-Munk (HMS) and the Papillon-Lef evre (PLS) syndromes. [25][26][27] Cathepsin C is a lysosomal cysteine protease acting as an activator of serine proteases of immune and inflammatory cells 24 and possibly as a modulator of epithelial differentiation.…”

Section: Palmoplantar Keratoderma With Prominent Mucosal Involvementmentioning

confidence: 99%

Hereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas – Diagnostic algorithm and principles of therapy

Guerra

Castori²,

Didona

et al. 2018

Acad Dermatol Venereol

View full text Add to dashboard Cite

Hereditary palmoplantar keratodermas (PPKs) comprise a large and heterogeneous group of disorders characterized by persistent thickening of the epidermis at palmar and plantar surfaces. Clinical and genetic features of isolated and complex PPKs have been reviewed in part I of this 2-part review. Here we focus on clinical and molecular classification of syndromic PPKs which are recognized by additional extracutaneous manifestations, in particular deafness, specific mucosal lesions, cardiomyopathy, inborn errors of metabolism, involvement of internal organs or disorders of sexual development. Other genetic diseases, which may show palmoplantar involvement, such as selected subtypes of hereditary epidermolysis bullosa, various hereditary ichthyoses and other keratinization disorders, several ectodermal dysplasias and some multisystem genetic disorders, are also briefly summarized. PPK diagnosis is based on inheritance pattern, age at onset, morphology, distribution and severity of hyperkeratosis, pattern of additional dermatological and systemic manifestations and laboratory findings. Molecular analysis is at present the gold standard to confirm the diagnosis in PPK forms due to mutations in known causative genes. No specific and curative therapy is currently available for PPKs which highly impair patients' quality of life. Topical treatments are symptomatic and offer only temporary relief. Among systemic treatments, retinoids improve disease symptoms in the majority of patients.

show abstract

Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients

Cited by 23 publications

References 47 publications

Neutrophil maturation rate determines the effects of dipeptidyl peptidase 1 inhibition on neutrophil serine protease activity

Neutrophil maturation rate determines the effects of dipeptidyl peptidase 1 inhibition on neutrophil serine protease activity

CTSC and Papillon–Lefèvre syndrome: detection of recurrent mutations in Hungarian patients, a review of published variants and database update

Hereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas – Diagnostic algorithm and principles of therapy

Contact Info

Product

Resources

About