Case report: Corticosteroids as an adjunct treatment for the management of liver abscess in Papillon–Lefevre syndrome: A report on two cases
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SUBMITTER: Basu S
PROVIDER: S-EPMC9530593 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Project description:Papillon-Lefèvre syndrome (PLS) is an autosomal recessive rare disease, main characteristics of which include palmoplantar hyperkeratosis and premature edentulism due to advanced periodontitis (formerly aggressive periodontitis). This study aimed to characterize the oral phenotype, including salivary parameters, and the salivary microbiome of three PLS sisters, comparatively. Two sisters were toothless (PLSTL1 and PLSTL2), and one sister had most of the teeth in the oral cavity (PLST). Total DNA was extracted from the unstimulated saliva, and the amplicon sequencing of the 16S rRNA gene fragment was performed in an Ion PGM platform. The amplicon sequence variants (ASVs) were obtained using the DADA2 pipeline, and the taxonomy was assigned using the SILVA v.138. The main phenotypic characteristics of PLS were bone loss and premature loss of primary and permanent dentition. The PLST sister presented advanced periodontitis with gingival bleeding and suppuration, corresponding to the advanced periodontitis as a manifestation of systemic disease, stage IV, grade C. All three PLS sisters presented hyposalivation as a possible secondary outcome of the syndrome. Interestingly, PLST salivary microbiota was dominated by the uncultured bacteria Bacterioidales (F0058), Fusobacterium, Treponema, and Sulfophobococcus (Archaea domain). Streptococcus, Haemophilus, and Caldivirga (Archaea) dominated the microbiome of the PLSTL1 sister, while the PLSTL2 had higher abundances of Lactobacillus and Porphyromonas. This study was the first to show a high abundance of organisms belonging to the Archaea domain comprising a core microbiome in human saliva. In conclusion, a PLST individual does have a microbiota different from that of the periodontitis' aggressiveness previously recognized. Due to an ineffective cathepsin C, the impairment of neutrophils probably provided a favorable environment for the PLS microbiome. The interactions of Bacteroidales F0058, Caldivirga, and Sulfophobococcus with the microbial consortium of PLS deserves future investigation. Traditional periodontal therapy is not efficient in PLS patients. Unraveling the PLS microbiome is essential in searching for appropriate treatment and avoiding early tooth loss.
| S-EPMC8427699 | biostudies-literature
Project description:Papillon-Lefèvre syndrome (PLS) results from mutations that inactivate cysteine protease cathepsin C (CTSC), which processes a variety of serine proteases considered essential for antimicrobial defense. Despite serine protease-deficient immune cell populations, PLS patients do not exhibit marked immunodeficiency. Here, we characterized a 24-year-old woman who had suffered from severe juvenile periodontal disease, but was otherwise healthy, and identified a homozygous missense mutation in CTSC indicative of PLS. Proteome analysis of patient neutrophil granules revealed that several proteins that normally localize to azurophil granules, including the major serine proteases, elastase, cathepsin G, and proteinase 3, were absent. Accordingly, neutrophils from this patient were incapable of producing neutrophil extracellular traps (NETs) in response to ROS and were unable to process endogenous cathelicidin hCAP-18 into the antibacterial peptide LL-37 in response to ionomycin. In immature myeloid cells from patient bone marrow, biosynthesis of CTSC and neutrophil serine proteases appeared normal along with initial processing and sorting to cellular storage. In contrast, these proteins were completely absent in mature neutrophils, indicating that CTSC mutation promotes protease degradation in more mature hematopoietic subsets, but does not affect protease production in progenitor cells. Together, these data indicate CTSC protects serine proteases from degradation in mature immune cells and suggest that neutrophil serine proteases are dispensable for human immunoprotection.
| S-EPMC4191054 | biostudies-literature
Project description:PurposePapilion-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder that involves palmoplantar keratosis (PK) and severe aggressive periodontitis. Cathepsin C (CTSC) gene mutations are etiologic for PLS, with more than 60 different mutations reported in different ethnic groups worldwide. The purpose of this study was to report a novel cathepsin C mutation in a Brazilian patient.MethodsA 4-year-old boy presented with aggressive periodontitis, recession, missing teeth, and hyperkeratosis of the palms of hands and soles. Peripheral blood samples were obtained from family members for genomic DNA isolation. The coding region and exon/intron boundaries of the CTSC gene were amplified and sequenced.ResultsThe patient had a PLS phenotype, which included PK and early-onset severe periodontitis. Sequence analysis showed a novel CTSC mutation (c.267-268del) present in the homozygous state.ConclusionThis report described a novel mutation in a family with Brazilian Papillon-Lefèvre syndrome and presented a review of all cathepsin C (65) mutations reported to date.
| S-EPMC4617240 | biostudies-literature
Project description:Papillon-Lefèvre syndrome (PLS) is a rare genetic disease that causes dermatological and dental symptoms that usually start from early age. Dermatological findings include hyperkeratoderma over the palms and soles that are usually thought of as persistent psoriasis at first. Dental findings include severe caries in the teeth that lead to premature dental loss. We present a case of an otherwise healthy seven-year-old child with classical presentation of PLS with both dermatological and dental findings. He first presented to the dermatology clinic when he was five years old brought by his parents complaining of dry scaly patches on the palm of the hands and soles of the feet. On further history it was found that he is a child of first-degree consanguinity, and he had these patches since he was four months old. On examination, he was found to have an erythematous hyperkeratotic skin plaques and papules with scales over the planter and palmar aspect of both hands with similar lesions observed on both feet, legs, scalp, and ears with nail pitting. The diagnosis of PLS was confirmed by whole-exome sequencing (WES) and the patient was started on acitretin capsules and started to show improvement.
| S-EPMC6942505 | biostudies-literature
Project description:ObjectivesPapillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder. These patients lose their teeth at a young age and are in need of prosthetic rehabilitation. The aim of this systematic review was to assess the success of dental implant placement in these patients.Materials and methodsAn electronic search was performed in PubMed Central, Scopus, and Web of Science using the keyword "Papillon-Lefèvre syndrome" AND "dental implant" OR "prosthodontics". Articles reporting implant placement in patients with PLS until July 2019 were included.ResultsAssessment of the included 11 articles reporting 15 cases showed 136 implant placements in these patients. Implant failure occurred in 3 patients (20 implants). The peri-implantitis and failure rate was higher in the maxilla. Meta-analysis showed the probability of failure to be 7% (95% confidence interval [CI] 0%-31%) for maxillary implants and 2% (95% CI 0%-9%) for mandibular implants. The follow-up time ranged between 1 and 20 years. Healing after bone graft and implant placement in these patients was uneventful.ConclusionDental implants may be a viable treatment option for PLS patients. Implantation can help preserve alveolar bone if the patients' immunological and growing conditions are well-considered and proper oral hygiene and compliance with the maintenance program are continued.
| S-EPMC7469965 | biostudies-literature
Project description:Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by early loss of teeth with hyperkeratosis of the palms and soles. Congenital insensitivity to pain with anhidrosis (CIPA) is a disorder of decreased pain sensation, decreased sweating, recurrent infections, and fever. Here, we report a 5-year-old girl born to consanguineous parents with a family history of a similarly affected sibling. The girl presented with early loss of teeth and palmoplantar hyperkeratosis, hence, provisionally diagnosed as PLS. Further clinical examination and detailed history taking shifted the diagnosis to CIPA. CIPA could be misdiagnosed as PLS. Congenital insensitivity to pain with anhidrosis, although rare, should be considered in the differential diagnosis of PLS.
| S-EPMC5683952 | biostudies-literature
Project description:BackgroundPLS 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 amino-terminus 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.MethodsPeripheral blood samples were obtained from individuals belonging to three Indian families with PLS for genomic DNA isolation. Exon-specific intronic primers were used to amplify DNA samples from individuals. PCR products were subsequently sequenced to detect mutations. PCR-SCCP and ASOH analyses were used to determine if mutations were present in normal control individuals.ResultsAll patients from three families had a classic PLS phenotype, which included palmoplantar keratosis and early-onset severe periodontitis. Sequence analysis of the CTSC gene showed three novel nonsense mutations (viz., p.Q49X, p.Q69X and p.Y304X) in homozygous state in affected individuals from these Indian families.ConclusionsThis study reported three novel nonsense mutations in three Indian families. These novel nonsense mutations are predicted to produce truncated dipeptidyl-peptidase I causing PLS phenotype in these families. A review of the literature along with three novel mutations reported here showed that the total number of mutations in the CTSC gene described to date is 41 with 17 mutations being located in exon 7.
| S-EPMC183830 | biostudies-literature
Project description:BackgroundPapillon-Lefèvre Syndrome (PLS) is a type IV genodermatosis caused by mutations in cathepsin C (CTSC), with a worldwide prevalence of 1-4 cases per million in the general population. In México, the prevalence of this syndrome is unknown, and there are few case reports. The diagnosis of twenty patients in the state of Sinaloa highlights the need to characterize this syndrome in Mexicans.MethodsTo understand the basis of PLS in Mexicans, the gene expression, enzymatic activity and mutational analysis of CTSC were assayed in nine PLS patients and their relatives. Frequencies of CTSC gene polymorphisms and HLA alleles were determined in these patients, their relatives, and the population.ResultsPatients showed normal CTSC gene expression, but a deep reduction (up to 85%) in enzymatic activity in comparison to unrelated healthy individuals. A novel loss-of-function mutation, c.203 T > G (p.Leu68Arg), was found in all patients, and some carried the polymorphism c.458C > T (p.Thr153Ile). Allelic frequencies in patients, relatives and controls were 88.89%, 38.24% and 0.25% for G (c.203 T > G); and 11.11%, 8.82% and 9.00% for T (c.458C > T). HLA-DRB1*11 was found significantly more frequent (P = 0.0071) in patients than controls (33.33% vs. 7.32%), with an estimated relative risk of 6.33.ConclusionsThe novel loss-of function mutation of CTSC gene (c.203 T > G) found in patients correlated with their diminished enzymatic activity, and HLA-DRB1*11 was found to be associated with PLS. The study of more PLS patients may give more insights into the etiology of the disease as well as its prevalence in México.
| S-EPMC3563609 | biostudies-literature
Project description:ObjectivesIn this study, we analyzed the whole exomes of CTSC gene in a family with history of PLS.Materials and methodsGenomic DNA was extracted from peripheral blood and genotype analysis was performed. The mutated protein sequence was used to find the best possible tertiary structure for homology modeling. The homology modeling of the novel mutation was then performed using the online Swiss-Prot server. The results were also analyzed for to verify its validity.ResultsThe analysis of CTSC gene elucidated a novel insertion GAC. The novel mutation was proved by analyzing 50 healthy control volunteers. Modeling of the novel found mutation in CTSC gene revealed structural defects that may have caused the functional abnormalities.ConclusionsThe structural analysis of the mutated protein model identifies changes in the stereo-chemical and the energy level of the mutated protein. Since this protein play a role in the activation of granule serine proteases from cytotoxic T lymphocytes, natural killer cells, mast cells, such structural defects may lead to its malfunction causing dysfunctioning of immune defense mechanisms.
| S-EPMC8404484 | biostudies-literature
Project description:Papillon-Lefevre syndrome (PLS; OMlM 245000) is an autosomal recessive disease caused by mutations in cathepsin C (CTSC) gene and is characterized by palmoplantar keratoderma, psoriasiform lesion over the extensor surfaces and gingivitis followed by loss of teeth. CTSC gene is expressed in several tissues including the skin and cells of the immune system. In the skin, CTSC plays a role in differentiation and desquamation, whereas in the immune system, it activates serine proteases.We analysed the molecular basis of PLS in a Pakistani family.Genomic DNA was isolated from the sample according to standard techniques. All exons of the CTSC gene with adjacent sequences of exon-intron borders were amplified by PCR and directly sequenced.We identified a novel deletion mutation designated c.2ldelG (Leu7PhefsX57) in exon 1 of the CTSC gene, which probably results in the absence of CTSC protein.Our data further expand the spectrum of mutations in the CTSC gene underlying PLS.
| S-EPMC2921986 | biostudies-literature