Mutations In Cathepsin Research Articles

Physics-Based Protein Networks Might Recover Effectful Mutations─a Case Study on Cathepsin G.

Molecular dynamics simulations have been remarkably effective for observing and analyzing structures and dynamics of proteins, with longer trajectories being computed every day. Still, often, relevant time scales are not observed. Adequately analyzing the generated trajectories can highlight the interesting areas within a protein such as mutation sites or allosteric hotspots, which might foreshadow dynamics untouched by the simulations. We employ a physics-based protein network and propose that such a network can adequately analyze the protein dynamics. The analysis is conducted on simulations of cathepsin G and neutrophil elastase, which are remarkably similar but with different specificities. However, a single mutation in cathepsin G recovers the specificity of neutrophil elastase. The physics-based network built on the interactions between residues instead of the distances can pinpoint the active triad in the proteins studied. Overall, the network seems to capture the structural behavior better than purely distance-based networks.

Challenges in the Surgical Orthopedic Treatment of Long Bone Fracture in a Rare Case of Pycnodysostosis

Pycnodysostosis is a rare autosomal recessive disorder caused by an inactivating mutation in cathepsin K (CTSK) and characterized by dysmorphic facial features, a short stature, acro-osteolysis, osteosclerosis with increased bone fragility, and delayed closure of cranial sutures. Although the satisfying healing potential, many issues exist in managing fractures in pycnodysostosis patients. In this paper, we report the challenges faced in managing a fracture of the femoral shaft in a 14-year-old boy coming from a low-income family. The patient was administered to the Paediatric Surgical Emergency Department of the Children's Hospital in Rabat for the management of a closed fracture of the left femur. Despite being of small stature with dysmorphic facial features, a prominent forehead, and brachydactyly, he never had a medical consultation before. The patient then underwent a surgical reduction. We attempted titanium elastic nail fixation, but metaphyseal drilling was not feasible due to the high bone density, and the narrow medullary canal eliminated this option. Therefore we opted for the palate fixation. Sclerotic bone made drilling extremely difficult. The postoperative fracture was successfully healed.

BG03 The first case of Haim–Munk syndrome in the UK

Abstract Haim–Munk syndrome (HMS) and Papillon–Lefevre syndrome (PLS) are rare, autosomal recessive palmoplantar keratodermas (PPKs) characterized by PPK and periodontal inflammation. They are phenotypic variants of clinically related syndromes caused by homozygous or compound heterozygous mutations in cathepsin C (CTSC) on chromosome 11q14. Specific features of HMS include pes planus, radiographic deformity of the fingers, arachnodactyly, acro-osteolysis and onychogryphosis. In contrast, PLS can be associated with neurological disorders, calcification of the dura mater, hyperhidrosis and susceptibility to infection. Fewer than 100 cases of HMS have been reported, the majority of which have come from the Cochin region of India. We describe the case of a phenotypic presentation of HMS, with a novel mutation in CTSC. To our knowledge, this is the first case of HMS in the UK. The patient was a 14-year-old male, born in Gujarat, India, to consanguineous, healthy parents. He migrated to the UK in his early teens and was referred for a specialist opinion of symptoms of ichthyosis and PPK, which had been present from the age of 8 years. He was treated with acitretin in India, before moving to the UK. Physical examination revealed transgradient PPK, generalized mild ichthyosis, periodontal inflammation, dystrophic fingernails and toenails, and marked deformities of the fingers, including contractures, subluxation and swan-neck deformities, with a degree of arthritis. Bilateral hand radiographs showed slender, long bones, with extension/flexion deformities at several sites but no erosions. Laboratory investigations revealed low iron, folate and vitamin D levels. Based on the clinical and radiographic findings, a diagnosis of HMS was made. The patient was continued on acitretin, soap substitutes, regular emollients, iron, folate and vitamin D supplementation and referred to occupational therapy for hand splinting. Next-generation sequencing identified an autosomal recessive, homozygous c.901G>A (p.Gly301Ser) variant of CTSC. A total of 75 mutations, in a diverse range of ethnic groups, have been reported in CTSC; the majority (97%) is reported in PLS. The variant seen in our patient has previously been reported in PLS; however, to our knowledge, it has not been associated with the HMS phenotype. This case details the first homozygous c.901G>A CTSC variant in a patient with HMS. To date, the genotype–phenotype correlations in PLS and HMS have not been established, largely due to the rarity of these conditions. This report adds to existing literature and expands on the understanding of clinical findings associated with CTSC mutations.

Cathepsin B p.Gly284Val Variant in Parkinson's Disease Pathogenesis.

Parkinson’s disease (PD) is generally considered a sporadic disorder, but a strong genetic background is often found. The aim of this study was to identify the underlying genetic cause of PD in two affected siblings and to subsequently assess the role of mutations in Cathepsin B (CTSB) in susceptibility to PD. A typical PD family was identified and whole-exome sequencing was performed in two affected siblings. Variants of interest were validated using Sanger sequencing. CTSB p.Gly284Val was genotyped in 2077 PD patients and 615 unrelated healthy controls from the Czech Republic, Ireland, Poland, Ukraine, and the USA. The gene burden analysis was conducted for the CTSB gene in an additional 769 PD probands from Mayo Clinic Florida familial PD cohort. CTSB expression and activity in patient-derived fibroblasts and controls were evaluated by qRT-PCR, western blot, immunocytochemistry, and enzymatic assay. The CTSB p.Gly284Val candidate variant was only identified in affected family members. Functional analysis of CTSB patient-derived fibroblasts under basal conditions did not reveal overt changes in endogenous expression, subcellular localization, or enzymatic activity in the heterozygous carrier of the CTSB variant. The identification of the CTSB p.Gly284Val may support the hypothesis that the CTSB locus harbors variants with differing penetrance that can determine the disease risk.

Novel frameshift CTSF mutation causing kufs disease type B mimicking frontotemporal dementia-parkinsonism

ABSTRACT Adult-onset neuronal ceroid lipofuscinoses (ANCLs, Kufs disease-KD) are rare, inherited, progressive, neurodegenerative, lysosomal storage diseases. Mutations in cathepsin F (CTSF) were linked to KD type B. Conversely, Frontotemporal dementia (FTD) is the second most common type of presenile dementia and Parkinsonism is a mostly common accompanying feature. Due to pronounced behavioral, cognitive, and motor features in the patients with KD type B, mutations in CTSF may resemble FTD-parkinsonism. Here, we present a case of KD type B with a novel homozygous frameshift pathogenic variant (p.Gly439Alafs*36) in the Cathepsin F (CTSF) gene presenting behavioral changes, cognitive disturbances and parkinsonism with a family history mimicking FTD-parkinsonism.

A Case Report: Papillon Lefevre Syndrome

Study Background: Papillon Lefevre Syndrome (PLS) is an autosomal recessive inherited genetic disorder characterized by palmoplantar hyperkeratosis and premature loss of deciduous and permanent teeth. Mutation of cathepsin C gene has been detected in the patient with PLS. In this case report, oral and radioghaphic findings of one PLS patient were discussed. 14 year old male patient diagnosed with PLS after radiographic, dermatologic and dental examination was referred to our clinic due to severe gingival inflamation and mobility. Severe gingival inflamation, alveolar bone resorption and multiple teeth loss due to periodontal reasons were observed. Mild palmar and moderate plantar hyperkeratosis were observed but no other systemic problems were detected. Methods: Non-surgical periodontal treatment was perfomed among multiple sessions and in each session subgingival tissues had been irrigated with %2 chlorhexidine irrigation solution. To reduce severe gingival inflammation antibiotherary has been prescribed. Hopeless teeth were extracted. Results: After non-surgical periodontal treatment and antibiotherary severe gingival inflammation was reduced but not eliminated completely, mobility score of some teeth reached to zero score, patient was motivated about oral hygiene and was taken into maintanence phases. After having extracted hopeless teeth patient was directed for prosthodontic rehabilitation. Conclusion: PLS is a rare autosomal recessive disorder. With PLS-specific dermatologic findings and characteristic periodontal view, it is possible to be able to identify the disease in its very early stages. Early diagnosis of the disease and institution of an appropriate periodontal and antimicrobial treatment might improve the prognosis.

Loss of cathepsin C enhances keratinocyte proliferation and inhibits apoptosis

Papillon–Lefèvre Syndrome is a rare autosomal recessive disorder characterized by rapidly progressive periodontitis and confined palmoplantar hyperkeratosis resulting from genetic mutations in cathepsin C (CTSC). The present study investigated the effect of CTSC on keratinocyte proliferation and apoptosis. HaCaT keratinocytes were transfected with wild-type CTSC and CTSC-targeted siRNAs to investigate the effects of CTSC expression on cell keratosis. Real-time PCR and Western blot analyses showed that the levels of loricrin and keratin (KRT)-1, but not KRT9, was correlated with CTSC expression. Loricrin was increased in the CTSC-overexpression group and downregulated in the CTSC-silenced group. A positive association between loricrin expression and cell apoptosis was detected in HaCaT keratinocytes. KRT1 was decreased in the CTSC-overexpression group and increased in the CTSC-silenced group. Prominent, punctuate KRT1 aggregates were present in CTSC-knockdown HaCaT cells. This study suggested that loss of CTSC contributes to keratinocyte hyperkeratosis via downregulation of loricrin and enhanced cell proliferation.

Mice heterozygous for cathepsin D deficiency exhibit mania-related behavior and stress-induced depression.

Mutations in cathepsin D (CTSD), an aspartic protease in the endosomal-lysosomal system, underlie congenital neuronal ceroid-lipofuscinosis (cNCL, also known as CLN10), a devastating neurodegenerative disease. CLN10 patients die within the first few days of life, and in the few patients who live into adulthood psychopathological symptoms have not been reported. Extensive neuropathology and altered neurotransmission have been reported in CTSD-deficient mice; however signs of neuropsychiatric behavior in these mice are not well characterized due to the severe movement disorder and premature death of the animal. In the present study, we show that heterozygous CTSD-deficient (CTSD HET) mice display an overall behavioral profile that is similar to human mania, including hyperlocomotion, d-amphetamine-induced hyperactivity, sleep-disturbance, and reduced anxiety-like behavior. However, under stressful conditions CTSD HET mice manifest depressive-like behavior, including anhedonia, behavioral despair, and enhanced learned helplessness. Chronic administration of lithium chloride or valproic acid, two clinically effective mood stabilizers, reverses the majority of these behavioral abnormalities. In addition, CTSD HET mice display stress-induced hypersecretion of corticosterone. These findings suggest an important role for CTSD in the regulation of mood stabilization.

A novel nonsense mutation in cathepsin C gene in an Egyptian patient presenting with Papillon–Lefèvre syndrome

BackgroundCathepsin C gene (CTSC) (MIM#602365) is a lysosomal cysteine proteinase coding gene which encodes for CTSC protein that plays a major role in the activation of granule serine proteases, particularly leukocyte elastase and granzymes A and B. This activity was proposed to play a role in epithelial differentiation and desquamation. Mutations that cause Disruption in the CTSC expression or function will result in loss of immunological response such as defects of phagocytic function and deregulation of localized polymorphonuclears response with subsequent clinical manifestation.AimThe aim of this study is to detect the mutation in CTSC gene expected to be the cause of Papillon Lefèvre syndrome (PLS) in an Egyptian patient clinically diagnosed as PLS and to characterize the clinical features.Patient and methodsA 5 year and 3 month old girl from the outpatient’s Oro-Dental Genetics clinic – National Research Center presented with the typical clinical findings of Papillon Lefevre syndrome. Genomic DNA was extracted from peripheral blood samples of the patient, her parents and 20 healthy Egyptian controls using standard procedures. All exons of the CTSC gene were amplified by PCR. Sequence analysis of the patient, her parents and controls was performed for mutation detection.ResultsMutation analysis of the CTSC gene in our patient revealed a novel homozygous nonsense mutation in exon 5 (W237X). Her parents revealed the presence of the same mutation in a heterozygous state. The 20 controls showed only the wild type sequence of all exons (no mutation).ConclusionThis study reported a novel nonsense mutation in the CTSC gene in an Egyptian patient. This novel nonsense mutation is predicted to produce truncated dipeptidyl-peptidase1 causing PLS phenotype in this patient.

Current research on pycnodysostosis.

Pycnodysostosis is a rare autosomal recessive disorder caused by an inactivating mutation in cathepsin K (CTSK) and characterized by dysmorphic facial features, a short stature, acroosteolysis, osteosclerosis with increased bone fragility, and delayed closure of cranial sutures. Patients usually present with short stature or dysmorphic features the Pediatric Endocrinology or Genetics clinics, with atypical fractures to the orthopedics clinics or hematological abnormalities to the hematology clinics. However, under-diagnosis or misdiagnosis of this condition is a major issue. Pycnodysostosis is not a life threatening condition, but craniosynostosis, frequent fractures, respiratory-sleep problems, and dental problems may cause significant morbidity. Although no specific treatment for this disorder has been described, patients should be followed for complications and treated accordingly. A specific treatment for the disorder must be established in the future to prevent complications and improve quality of life for patients in the current era of advanced molecular research.

Protein modeling of cathepsin C mutations found in Papillon–Lefèvre syndrome

BackgroundPapillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by hyperkeratosis involving the palms, soles, elbows, and knees followed by periodontitis, destruction of alveolar bone, and loss of primary and permanent teeth. Mutations of the lysosomal protease cathepsin C gene (CTSC) have been shown to be the genetic cause of PLS. This study analyzed CTSC mutations in five Iranian families with PLS and modeled the protein for mutations found in two of them. MethodsDNA analysis was performed by direct automated sequencing of genomic DNA amplified from exonic regions and associated splice intron site junctions of CTSC. RFLP analyses were performed to investigate the presence of previously unidentified mutation(s) in control groups. Protein homology modeling of the deduced novel mutations (P35 delL and R272P) was performed using the online Swiss-Prot server for automated modeling and analyzed and tested with special bioinformatics tools to better understand the structural effects caused by mutations in cathepsin C protein (CTSC). ResultsSix Iranian patients with PLS experienced premature tooth loss and palm plantar hyperkeratosis. Sequence analysis of CTSC revealed a novel mutation (P35delL) in exon 1 of Patient 1, and four previously reported mutations; R210X in Patient 2, R272P in Patient 3, Q312R in two siblings of family 4 (Patients 4 and 5), and CS043636 in Patient 6. RFLP analyses revealed different restriction fragment patterns between 50 healthy controls and patients for the P35delL mutation. Modeling of the mutations found in CTSC, P35delL in Patient 1 and R272P in Patient 3 revealed structural effects, which caused the functional abnormalities of the mutated proteins. ConclusionsThe presence of this mutation in these patients provides evidence for founder CTSC mutations in PLS. This newly identified P35delL mutation leads to the loss of a leucine residue in the protein. The result of this study indicates that the phenotypes observed in these two patients are likely due to CTSC mutations. Also, structural analyses of the altered proteins identified changes in energy and stereochemistry that likely alter protein function.

Central extrapontine myelinolysis appearing as acute parkinsonism

Central extrapontine myelinolysis appearing as acute parkinsonism

Novel mutations in cathepsin D in juvenile onset neuronal ceroid lipofuscinosis

Background: Mutations in cathepsin D (CTSD) have been previously reported in patients with neuronal ceroid lipofuscinosis (CLN10). To date only 7 mutations have been reported in four families with an NCL-like illness. We report the identification of two novel homozygous mutations in two families with juvenile onset ataxia and retinitis pigmentosa.

Genetic Mapping in Papillon-Lefèvre Syndrome: A Report of Two Cases

Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive heterogeneous trait which is characterized by erythematous palmoplantar hyperkeratosis, early-onset periodontitis, and associated calcification of dura mater. The etiology of PLS is multifactorial with genetic, immunological, and microbial factors playing a role in etiopathogenesis. Recently identified genetic defect in PLS has been mapped to chromosome 11q14–q21, which involves mutations of cathepsin C. This paper presents a report of 2 cases of Papillon-lefevre syndrome in which diagnosis is based on clinical presentation and genetic mapping.

A Germline Mutation in Cathepsin B in a Child with ALL Points towards a Key Role for This Enzyme in L-Asparaginase Pharmacokinetics.

AbstractAbstract 2458▪▪This icon denotes a clinically relevant abstractThe bacterially derived enzyme L-Asparaginase (ASNase) is a key component in the multidrug therapy regimens used worldwide to treat pediatric and adult patients with acute lymphoblastic leukemia (ALL), however little is known about the molecular mechanisms that control the pharmacokinetics of this therapeutic protein. As a result, many patients who receive a standardized dose either exceed or do not reach the desired serum concentration. While elevated serum levels are associated with an increase in treatment related morbidity, underexposure seriously compromises therapeutic benefits.In search of molecular factors that determine ASNase turnover in vivo, we investigated a patient with strongly aberrant clearance kinetics. This 3-year old female diagnosed with common ALL suffered from severe ASNase-induced adverse events upon treatment with ErwiniaSNase as a result of strongly elevated serum ASNase levels. Pharmacokinetics data showed a severely delayed ASNase clearance. As a result, serum ASNase levels accumulated to intolerable levels upon repeated administration of the drug. We isolated DNA from peripheral blood mononuclear cells and buccal cells of this patient and performed targeted sequencing on genes suggested to be involved in ASNase clearance. We identified a novel heterozygous mutation in the gene encoding Cathepsin B in the germline of this patient. The mutant allele shows a deletion of a single codon, leading to a deletion of a lysine residue in the C terminus of the protein. We generated an EBV LCL cell line from this patients which showed a 75% reduction in Cathepsin B activity, relative to controls, indicating that this heterozygous mutation has a profound effect on the total Cathepsin B activity.Cathepsin B is normally synthesized as a 37 kD pre-pro enzyme and is processed in a two step process into a mature 2-chain active form. During this process, the protein is transported to the lysosome where it exerts its primary function. Using a combination of biochemical and imaging experiments we show that the mutant Cathepsin B cannot be processed into the mature form and is retained in the endoplasmatic reticulum. ASNase degradation assays demonstrate that this mutant form of Cathepsin B shows a diminished protease activity towards both E.coli and Erwinia ASNase, consistent with the reduced clearance observed in our patient.Cathepsin B and other cellular proteases are either actively secreted or released into the serum as a result of cell lysis. Although we find a variable low but detectable activity of Cathepin B in serum samples, all tested preparations of ASNase were stable upon prolonged incubation in serum, suggesting that serum components are not contributing to ASNase clearance in vivo. Hence, we propose that cellular uptake and subsequent proteolytic degradation of ASNase is the primary mechanism of clearance.In conclusion, we have identified a mutation in protease Cathepsin B and provide evidence that this mutation results in a loss of protease function towards ASNase, which can explain the strongly delayed clearance of ASNase in the patient. Our data suggest that differences in Cathepsin B activity may contribute to the large inter-patient variability in ASNase pharmacokinetics. Furthermore, given the role of Cathepsin proteases in antigen presentation, Cathepsin B may not only provide a target for predicting or controlling ASNase clearance kinetics but inhibition of Cathepsin may also prevent or delay the formation of inhibitory antibodies. Disclosures:Boos:European Erwinase Providers (EUSAPharm): Speakers Bureau; Medac: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lanvers-Kaminsky:Medac: Speakers Bureau.

Cathepsin C Gene 5′-Untranslated Region Mutation in Papillon-Lefèvre Syndrome

Background: Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by palmoplantar keratoderma together with a severe form of generalized aggressive periodontitis and associated with mutations in cathepsin C gene (CTSC). Objective: To investigate the clinical and mutational characteristics of 6 PLS patients from 4 unrelated Slovenian families. Methods:CTSC mutational and functional analyses were performed. Results: In all patients, a novel homozygous substitution, c.-55C>A, in the CTSC 5′-untranslated region (UTR) was detected on genomic DNA level and confirmed by mRNA analysis, resulting in the almost complete loss of CTSC mRNA expression and CTSC activity. In silico analysis revealed the potential of the mutation to disrupt putative transcription factor binding sites (TFBSs) for AP-2 and Sp families of transcription factors. Conclusion: Identification of a novel CTSC 5′-UTR mutation together with a severe reduction of CTSC mRNA expression and virtually nonexistent CTSC activity was suggestive of a novel mechanism of TFBS dysfunction associated with PLS.

Isolation and Characterization of Dental Pulp Stem Cells from a Patient with Papillon–Lefèvre Syndrome

IntroductionPapillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by immune dysregulation because of a mutation in cathepsin c gene, resulting in hyperkeratosis of the palms, soles, elbows, and knees combined with premature loss of the primary and permanent dentitions. Periodontal tissue abnormalities in PLS patients were reported previously. However, less is known about dental pulp tissue derived cells of PLS patients. This study aimed to show stem cell potential of PLS dental pulp stem cells (DPSCs) and provide new evidence regarding the pathophysiology of the disease. MethodsDPSCs were characterized by using flow cytometry and immunocytochemistry. They were also induced to differentiate into adipogenic, osteogenic, chondrogenic, odontogenic, and myogenic cells. ResultsThe results revealed that PLS DPSCs are stained positive for mesenchymal stem cells surface markers CD29, CD73, CD90, CD105, and CD166. PLS DPSCs were able to differentiate into adipogenic, osteogenic, chondrogenic, and odontogenic cell types properly. PLS DPSCs expressed embryonic stem cell markers Oct4, Sox2, cMYc, and Klf4 and showed similar proliferation rate compared with DPSCs isolated from healthy young controls. Interestingly, it was found that unlike the healthy DPSCs, PLS DPSCs are not able to form myotubes with correct morphology. ConclusionsThese data are being reported for the first time; therefore, they might provide new insights to the pathology of the disease. Our results suggest that the PLS DPSCs might be an autologous stem cell source for PLS patients for cellular therapy of alveolar bone defects and other dental tissue abnormalities observed in PLS.

Diminished asparaginase turnover due to a germ-line mutation in cathepsin B.

9550 Background: ASNase is a key component of multi-agent chemotherapy protocols used in the treatment of pediatric as well as adult acute lymphoblastic leukemia (ALL). Patients that are treated according to fixed shedules show a strong inter individual variation in serum ASNase levels. While underexposure may compromise therapeutic benefits, strongly elevated serum levels may lead to serious adverse effects. In at least 10% of the patients the desired ASNase levels are either not reached or exceeded. Therefore our understanding of ASNase dynamics in vivo needs to be improved. Here we describe the identification of a novel mutation in the gene encoding Cathepsin B to diminished ASNase turnover in a pediatric patient with ALL. Methods: Sequencing, biochemical experiments and immunofluorescence. Results: A 3-year-old girl diagnosed with ALL experienced serious toxicity in the form of hyperammonemic encephalopathy during treatment with ASNase derived from Erwinia chrysantemi. Pharmacokinetic data showed a strongly delayed clearance of the ASNase, which with the standard treatment protocol resulted in extremely high serum ASNase levels. Plasmapheresis was performed and dosage frequencies were adjusted to improve the clinical status of the patient. No underlying metabolic disorder could be diagnosed. Based on a previous report describing the role of proteases in degradation of ASNase in vitro, we hypothesized that the cysteine protease Cathepsin B might be implicated in the strongly reduced clearance of ASNase in this patient. Sequencing of the open reading frame of the Cathepsin B gene (CTSB) revealed a single codon deletion in the germline of the patient, affecting a lysine residue in the carboxy terminus of the protein. Immunofluorescence and biochemical experiments show that this single amino acid deletion leads to a protein product that is retained in the endoplasmic reticulum and is inefficiently processed. Conclusions: ASNase degradation assays show that the mutant Cathepsin B has lost its ability to efficiently degrade ASNase which could explain the high levels of ASNase as observed in our patient.Together, these findings suggest that variations in Cathepsin B activity may influence serum ASNase levels in the patients.

Rehabilitation of three siblings with Papillon-Lefevre syndrome

Papillion-Lefevre Syndrome is a rare autosomal recessive disorder characterized by severe early onset periodontopathia and palmoplantar hyperkeratosis leading to premature loss of primary and permanent dentition. PLS is caused by mutations in cathepsin C (CTSC) gene. It is transmitted with an estimated frequency of one to four per million individuals. In this case report, we present clinical and other relevant investigations of three siblings with symptoms typical of Papillion-Lefevre Syndrome. The three siblings were born of a second-degree consanguineous marriage, where the parents were first cousins. All the siblings reported with mobility, eventually leading to loss of teeth and masticatory inefficiency. All showed hyperkeratosis of palms and soles, with youngest sibling showing mild to severe form of severe generalized periodontal destruction. The elder two siblings were given dentures. The youngest sibling is undergoing periodontal therapy and has received partial dentures for missing teeth. Clinical Relevance to Interdisciplinary Dentistry PLS is a rare autosomal disorder which needs to be diagnosed early. Timely intervention of periodontal therapy helps in decreasing the loss of teeth at an early stage. This facilitates growth of jaws and eventual successful placement of implants. Dermatological treatment and psychological counseling are also mandatory Helps to educate the parents and family members. Needs team approach for successful outcome.

Papillon - lefèvre syndrome: A case report of two siblings

Papillon-Lefèvre Syndrome (PLS) is an autosomal recessive disorder characterized by severe periodontitis and palmoplantar hyperkeratosis. Microbial lipopolysaccharides and mutations of cathepsin C gene has been suggested as the most probable etiological factors for PLS. This article presents a case of a thirteen year old female and her sibling suffering from the disease.