205 results on '"Papillon-Lefevre disease"'
Search Results
2. Oral Phenotype and Salivary Microbiome of Individuals With Papillon–Lefèvre Syndrome
- Author
-
Giulia Melo Lettieri, Luander Medrado Santiago, Giancarlo Crosara Lettieri, Luiz Gustavo dos Anjos Borges, Letícia Marconatto, Laudimar Alves de Oliveira, Nailê Damé-Teixeira, Loise Pedrosa Salles, and HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
- Subjects
Microbiology (medical) ,Saliva ,cathepsin C ,Immunology ,Papillon–Lefèvre syndrome ,Microbiology ,Papillon-Lefevre Disease ,Cellular and Infection Microbiology ,periodontal infection ,RNA, Ribosomal, 16S ,medicine ,Humans ,Aggressive periodontitis ,Microbiome ,periodontitis ,Original Research ,Periodontitis ,saliva ,biology ,Periodontitis as a manifestation of systemic disease ,Microbiota ,microbiology ,medicine.disease ,biology.organism_classification ,QR1-502 ,Phenotype ,Infectious Diseases ,Aggressive Periodontitis ,Papillon–Lefèvre disease ,Fusobacterium ,Intercellular Signaling Peptides and Proteins ,Female - Abstract
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 bacteriaBacterioidales(F0058),Fusobacterium,Treponema, andSulfophobococcus(Archaeadomain).Streptococcus,Haemophilus, andCaldivirga(Archaea) dominated the microbiome of the PLSTL1 sister, while the PLSTL2 had higher abundances ofLactobacillusandPorphyromonas. This study was the first to show a high abundance of organisms belonging to theArchaeadomain 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 ofBacteroidalesF0058,Caldivirga, andSulfophobococcuswith 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.
- Published
- 2021
3. 'Oral Manifestations of Patients with Inherited Defect in Phagocyte Number or Function' a systematic review
- Author
-
Ahmad Reza Shamshiri, Nima Rezaei, Heliya Ziaei, and Arghavan Tonkaboni
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Neutropenia ,Phagocyte ,GATA2 Deficiency ,Primary Immunodeficiency Diseases ,Immunology ,Granulomatous Disease, Chronic ,Papillon-Lefevre Disease ,medicine ,Immunology and Allergy ,Humans ,Congenital Neutropenia ,Respiratory Burst ,Periodontitis ,Review study ,Phagocytes ,business.industry ,medicine.disease ,medicine.anatomical_structure ,Primary immunodeficiency ,Oral health care ,Female ,business ,Mouth Diseases - Abstract
Introduction Inherited phagocyte defects are one of the subgroups of primary immunodeficiency diseases (PIDs) with various clinical manifestations. As oral manifestations are common at the early ages, oral practitioners can have a special role in the early diagnosis. Materials and methods A comprehensive search was conducted in this systematic review study and data of included studies were categorized into four subgroups of phagocyte defects, including congenital neutropenia, defects of motility, defects of respiratory burst, and other non-lymphoid defects. Results Among all phagocyte defects, 12 disorders had reported data for oral manifestations in published articles. A total of 987 cases were included in this study. Periodontitis is one of the most common oral manifestations. Conclusion There is a need to organize better collaboration between medical doctors and dentists to diagnose and treat patients with phagocyte defects. Regular dental visits and professional oral health care are recommended from the time of the first primary teeth eruption in newborns.
- Published
- 2021
4. Clinical and molecular analysis in Papillon–Lefèvre syndrome
- Author
-
Florence J. M. Cuadra‐Zelaya, Ricardo D. Coletta, Renato Corrêa Viana Casarin, Renato Assis Machado, Hercílio Martelli-Júnior, Mônica Grazieli Corrêa, Roseli Teixeira de Miranda, and Francisco Humberto Nociti
- Subjects
Adult ,Male ,Models, Molecular ,Adolescent ,Hyperkeratosis ,Papillon–Lefèvre syndrome ,Biology ,medicine.disease_cause ,Cathepsin C ,Young Adult ,Papillon-Lefevre Disease ,Genetics ,medicine ,Humans ,Expressivity (genetics) ,Child ,Genetics (clinical) ,Cathepsin ,Mutation ,medicine.disease ,Phenotype ,Child, Preschool ,Mutation testing ,Female - Abstract
Papillon-Lefevre syndrome (PLS; MIM#245000) is a rare recessive autosomal disorder characterized by palmar and plantar hyperkeratosis, and aggressively progressing periodontitis leading to premature loss of deciduous and permanent teeth. PLS is caused by loss-of-function mutations in the CTSC gene, which encodes cathepsin C. PLS clinical expressivity is highly variable and no consistent genotype-phenotype correlation has been demonstrated yet. Here we report the clinical and genetic features of five PLS patients presenting a severe periodontal breakdown in primary and permanent dentition, hyperkeratosis over palms and soles, and recurrent sinusitis and/or tonsillitis. Mutation analysis revealed two novel homozygous recessive mutations (c.947T>C and c.1010G>C) and one previous described homozygous recessive mutation (c.901G>A), with parents carrying them in heterozygous, in three families (four patients). The fourth family presented with the CTSC c.628C>T mutation in heterozygous, which was inherited maternally. Patient carrying the CTSC c.628C>T mutation featured classical PLS phenotype, but no PLS clinical characteristics were found in his carrier mother. All mutations were found to affect directly (c.901G>A, c.947T>C, and c.1010G>C) or indirectly (c.628C>T, which induces a premature termination) the heavy chain of the cathepsin C, the region responsible for activation of the lysosomal protease. Together, these findings indicate that both homozygous and heterozygous mutations in the cathepsin C heavy chain domain may lead to classical PLS phenotype, suggesting roles for epistasis or gene-environment interactions on determination of PLS phenotypes.
- Published
- 2019
5. Identification of putative genetic modifying factors that influence the development of Papillon-Lefévre or Haim-Munk syndrome phenotypes
- Author
-
B. Fábos, Gábor Németh, Nikoletta Nagy, Márta Széll, Klaudia Farkas, É M Pap, and L. Tóth
- Subjects
Male ,Haim–Munk syndrome ,DNA Mutational Analysis ,Mutation, Missense ,Dermatology ,Papillon–Lefèvre syndrome ,Biology ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Cathepsin C ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Papillon-Lefevre Disease ,medicine ,Missense mutation ,Humans ,Gene ,Exome sequencing ,Genetics ,Mutation ,Acro-Osteolysis ,medicine.disease ,Phenotype ,030220 oncology & carcinogenesis ,Female ,Signal Transduction - Abstract
Background Papillon-Lefevre syndrome (PLS; OMIM 245000) and Haim-Munk syndrome (HMS; OMIM 245010), which are both characterized by palmoplantar hyperkeratosis and periodontitis, are phenotypic variants of the same disease caused by mutations of the cathepsin C (CTSC) gene. Aim To identify putative genetic modifying factors responsible for the differential development of the PLS or HMS phenotypes, we investigated two Hungarian patients with different phenotypic variants (PLS and HMS) but carrying the same homozygous nonsense CTSC mutation (c.748C/T; p.Arg250X). Methods To gain insights into phenotype-modifying associations, whole exome sequencing (WES) was performed for both patients, and the results were compared to identify potentially relevant genetic modifying factors. Results WES revealed two putative phenotype-modifying variants: (i) a missense mutation (rs34608771) of the SH2 domain containing 4A (SH2D4A) gene encoding an adaptor protein involved in intracellular signalling of cystatin F, a known inhibitor of the cathepsin protein, and (ii) a missense variant (rs55695858) of the odorant binding protein 2A (OBP2A) gene, influencing the function of the cathepsin protein through the glycosyltransferase 6 domain containing 1 (GLT6D1) protein. Conclusion Our study contributes to the accumulating evidence supporting the clinical importance of phenotype-modifying genetic factors, which have high potential to aid the elucidation of genotype-phenotype correlations and disease prognosis.
- Published
- 2020
6. Papillon-Lefèvre syndrome: report of six patients and identification of a novel mutation
- Author
-
Filippo Beleggia, Burak Tekin, Eli Sprecher, Deniz Yucelten, and Ofer Sarig
- Subjects
Male ,0301 basic medicine ,Adolescent ,Turkey ,Mutation, Missense ,Dermatology ,Papillon–Lefèvre syndrome ,Severity of Illness Index ,Genetic analysis ,Cathepsin C ,Sampling Studies ,Young Adult ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Papillon-Lefevre Disease ,Rare Diseases ,0302 clinical medicine ,medicine ,Humans ,Missense mutation ,Child ,Gene ,Periodontitis ,Genetics ,business.industry ,Genetic Carrier Screening ,Genodermatosis ,medicine.disease ,Pedigree ,030104 developmental biology ,Palmoplantar keratoderma ,Child, Preschool ,Female ,business - Abstract
Papillon-Lefevre syndrome is an autosomal recessive genodermatosis typically manifesting with the constellation of palmoplantar keratoderma and progressive early-onset periodontitis. The cutaneous phenotype can be strikingly psoriasiform, possibly posing a diagnostic challenge. This rare disorder is caused by loss-of-function mutations in the CTSC gene, which encodes cathepsin C. We report six patients with Papillon-Lefevre syndrome from five consanguineous Turkish families, in whom genetic analysis of the CTSC gene revealed four recurrent mutations (c.415G>A; c.1015C>T; c.1019A>G; and c.103-105delCTG) and a novel missense mutation (c.117G>T) in the homozygous state.
- Published
- 2016
7. Scanning Electron-Microscopy of Plaque in Papillon-Lefèvre Syndrome
- Author
-
Fermin A. Carranza, Michael G. Newman, and Jorge Jung
- Subjects
Pathology ,medicine.medical_specialty ,Bacilli ,Root surface ,Dental Plaque ,Gingiva ,Papillon–Lefèvre syndrome ,Biology ,medicine.disease_cause ,Microbiology ,Papillon-Lefevre Disease ,Keratoderma, Palmoplantar ,medicine ,Humans ,In patient ,Cementum ,Child ,Subgingival plaque ,Bacteria ,Tooth surface ,Mycoplasma ,medicine.disease ,biology.organism_classification ,medicine.anatomical_structure ,Child, Preschool ,Microscopy, Electron, Scanning ,Periodontics ,Female - Abstract
Supra and subgingival plaque associated with periodontal lesions in patients with Papillon-Lefèvre syndrome were studied by examining extracted teeth and associated soft tissue by scanning electron and light microscopy. Four zones of plaque were described according to their location along the tooth surface. Supragingivally, cocci, filamentous bacilli and "corncob" formations were seen. Fusiform bacilli colonized the surface of supragingival plaque on the root surface. Subgingival sites, particularly apical areas, had numerous spirochetes adherent to the plaque surface as well as directly to the cementum surface. Microcolonies of bacteria, probably Mycoplasma, could be seen in the subgingival plaque. The findings of a potentially pathogenic plaque, attached subgingival spirochetes and microcolony formation may have important therapeutic and research implications.
- Published
- 2018
8. Autophagic dysfunction in patients with papillon-lefevre syndrome is restored by recombinant cathepsin C treatment
- Author
-
David Cotán, Lourdes Román-Malo, Pedro Bullón, Beatriz Castejón-Vega, Tamara Y. Forbes-Hernandez, José L. Quiles, Maurizio Battino, Antonio J. Pérez-Pulido, Mario D. Cordero, José Antonio Sánchez-Alcázar, Alfonso Varela-López, Francesca Giampieri, and Maripaz Jiménez-Guerrero
- Subjects
Adult ,Male ,0301 basic medicine ,Autophagosome ,Proteases ,Insecta ,Immunology ,Papillon–Lefèvre syndrome ,Cathepsin B ,Cathepsin C ,Young Adult ,03 medical and health sciences ,Papillon-Lefevre Disease ,medicine ,Papillon-Lefevre syndrome ,Autophagy ,Animals ,Humans ,Immunology and Allergy ,Cells, Cultured ,Skin ,Cathepsin ,Chemistry ,Inflammasome ,Fibroblasts ,medicine.disease ,Molecular biology ,Recombinant Proteins ,030104 developmental biology ,Mutation ,Female ,Lysosomal permeabilization ,Lysosomes ,Reactive Oxygen Species ,medicine.drug - Abstract
Background: Cathepsin C (CatC) is a lysosomal enzyme involved in activation of serine proteases from immune and inflammatory cells. Several loss-of-function mutations in the CatC gene have been shown to be the genetic mark of Papillon-Lef evre syndrome (PLS), a rare autosomal recessive disease characterized by severe early-onset periodontitis, palmoplantar hyperkeratosis, and increased susceptibility to infections. Deficiencies or dysfunction in other cathepsin family proteins, such as cathepsin B or D, have been associated with autophagic and lysosomal disorders. Objectives: Here we characterized the basis for autophagic dysfunction in patients with PLS by analyzing skin fibroblasts derived from patients with several mutations in the CatC gene and reduced enzymatic activity. Methods: Skin fibroblasts were isolated from patients with PLS assessed by using genetic analysis. Authophagic flux dysfunction was evaluated by examining accumulation of p62/SQSTM1 and a bafilomycin assay. Ultrastructural analysis further confirmed abnormal accumulation of autophagic vesicles in mutant cells. A recombinant CatC protein was produced by a baculovirus system in insect cell cultures. Results: Mutant fibroblasts from patients with PLS showed alterations in oxidative/antioxidative status, reduced oxygen consumption, and a marked autophagic dysfunction associated with autophagosome accumulation. These alterations were accompanied by lysosomal permeabilization, cathepsin B release, and NLR family pyrin domain containing 3 (NLRP3) inflammasome activation. Treatment of mutant fibroblasts with recombinant CatC improved cell growth and autophagic flux and partially restored lysosomal permeabilization. Conclusions: Our data provide a novel molecular mechanism underlying PLS. Impaired autophagy caused by insufficient lysosomal function might represent a new therapeutic target for PLS. (J Allergy Clin Immunol 2018;142:1131-43.), Proyecto de Investigacion de Excelencia de la Junta de Andalucia CTS113, Instituto de Salud Carlos III PI16/00786, Fondo Europeo de Desarrollo Regional (FEDER-Union Europea)
- Published
- 2018
9. A novel large deletion combined with a nonsense mutation in a Chinese child with Papillon-Lefèvre syndrome
- Author
-
Weibin Sun, Li Chen, Feng Yan, Ye Wang, W. L. Wu, Bin Chen, Xuliang Chen, and Long Yi
- Subjects
DNA Mutational Analysis ,Nonsense mutation ,Papillon–Lefèvre syndrome ,Gene mutation ,Cathepsin C ,Tooth Loss ,030207 dermatology & venereal diseases ,03 medical and health sciences ,Papillon-Lefevre Disease ,0302 clinical medicine ,Asian People ,Radiography, Panoramic ,Humans ,Point Mutation ,Medicine ,Gene ,Sequence Deletion ,Sequence (medicine) ,Genetics ,business.industry ,Point mutation ,030206 dentistry ,medicine.disease ,Palmoplantar keratoderma ,Aggressive Periodontitis ,Codon, Nonsense ,Child, Preschool ,Mutation (genetic algorithm) ,Periodontics ,Female ,business - Abstract
Background and objective Papillon-Lefevre Syndrome (PLS) is a rare autosomal recessive hereditary disease (MIM245000). The syndrome is characterized by palmoplantar keratoderma and early onset periodontitis, caused by CTSC gene mutation. The mutation in CTSC previously reported is mainly point mutations. Large deletion in the CTSC gene has not yet been reported. Material and methods We collected 5 mL peripheral blood from a patient with PLS and her family members and used the direct sequencing method to perform CTSC bidirectional sequencing. We also used FISH to analyze the approximate locations of the ends of the missing fragment and then determined the fragment sequence through direct sequencing. Results The result demonstrated that the patient have a 110 kb deletion (Chr11: 88032292: 88142997(NC_000011)) combined with a nonsense mutation (Gln182Ter) in this gene. Conclusion Our study reveals a compound mutation consisting of a large deletion and a nonsense mutation, which provides a new insight in the mutation type of CTSC gene.
- Published
- 2015
10. Combined orthodontic and periodontic treatment in a child with Papillon Lefèvre syndrome
- Author
-
Maha Al-Sarheed and Fares S Al-Sehaibany
- Subjects
Periodontal treatment ,Combination therapy ,Orthodontic Brackets ,Dentistry ,Case Report ,Malocclusion, Angle Class I ,Papillon–Lefèvre syndrome ,Papillon-Lefevre Disease ,Treatment plan ,medicine ,Extraoral Traction Appliances ,Humans ,Combined Modality Therapy ,Child ,Dental Care ,Therapeutic Irrigation ,Permanent teeth ,Orthodontics ,business.industry ,General Medicine ,medicine.disease ,Anti-Bacterial Agents ,Regimen ,Dental Scaling ,Female ,Malocclusion ,business - Abstract
A 9-year-old girl with Papillon-Lefèvre syndrome (PLS) was treated orthodontically 24 months after the start of mechanical and antibiotic therapy in adjunct with periodontal treatment every 6 weeks. After achieving stable periodontal conditions, orthodontic treatment was commenced to correct the teeth position, facial profile, and maxillary protraction. Following the combination therapy and a failure to detect Actinobacillus actinomycetemcomitans from any site in the oral cavity, orthodontic treatment with a fixed appliance was performed aside from creating space for eruption of permanent teeth. We found that combined periodontal and orthodontic treatment of PLS may be successful with a complex interdisciplinary regimen and close follow up. This is a 2-year follow-up case report of a girl with PLS. Orthodontic and periodontic therapy were offered using combined treatments of orthodontic and periodontal with the benefit of prosthodontic consultation, resulting in a treatment plan.
- Published
- 2015
11. One mutation, two phenotypes: a single nonsense mutation of theCTSCgene causes two clinically distinct phenotypes
- Author
-
Lajos Kemény, B. Fábos, Márta Széll, Kornélia Tripolszki, Nikoletta Nagy, Péter Vályi, Klaudia Farkas, Adrienn Sulák, L. Tóth, and Katalin Nagy
- Subjects
Adult ,Male ,0301 basic medicine ,Genotype ,media_common.quotation_subject ,Nonsense mutation ,Nonsense ,Dermatology ,Biology ,medicine.disease_cause ,Cathepsin C ,03 medical and health sciences ,Papillon-Lefevre Disease ,medicine ,Humans ,Gene ,media_common ,Genetics ,Mutation ,Acro-Osteolysis ,Haplotype ,Phenotype ,Molecular biology ,030104 developmental biology ,Codon, Nonsense ,Female - Abstract
Summary Background Papillon–Lefevre syndrome (PLS; OMIM 245000) and Haim–Munk syndromes (HMS; OMIM 245010) are phenotypic variants of the same rare disease caused by mutations of the cathepsin C (CTSC) gene, and they exhibit autosomal recessive inheritance. Aims To identify diseases caused by mutations of the CTSC gene in two Hungarian patients and to perform haplotype analysis to elucidate any familial relationship between them. Methods Mutation screening and polymorphism analysis were performed by direct sequencing of the CTSC gene. Results Mutation screening of the CTSC gene from the two patients revealed the presence of the same homozygous nonsense mutation (c.748C/T; p.Arg250X). However, one patient exhibited the PLS phenotype and the other the HMS phenotype. Although these patients were not aware that they were related, haplotype analysis, especially the genotypes of the rs217116 and the rs217115 polymorphisms, clearly indicated that the patients carry the same haplotype, whereas the unrelated healthy controls carried several different haplotypes. Conclusions Our results demonstrate that PLS and HMS are phenotypic variants of the same disease and, additionally, exclude the presence of a putative genetic modifier factor within the CTSC gene that is responsible for the development of the two phenotypes. We suggest that this putative genetic modifier factor is located outside the CTSC gene, or alternatively, that the development of the different phenotypes is the consequence of different environmental or lifestyle factors.
- Published
- 2015
12. Papillon-Lefèvre syndrome: A series of three cases in the same family and a literature review
- Author
-
Jasbir D, Upadhyaya, Dustin, Pfundheller, Mohammed N, Islam, and Indraneel, Bhattacharyya
- Subjects
Diagnosis, Differential ,Consanguinity ,Papillon-Lefevre Disease ,Yemen ,Adolescent ,Humans ,Female ,Child - Abstract
Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder that exhibits palmoplantar keratosis and early severe periodontitis. The oral disease affects both the primary and permanent dentitions leading to premature exfoliation of teeth. Various etiologic factors, such as genetic mutations, immunologic alterations, and bacteria have been implicated in PLS. Genetic mutations leading to the loss of function of cathepsin C (CTSC) gene, located on chromosome 11q14, is considered pivotal in this condition. The present case series describes PLS in three siblings, with consanguineously married parents, who live in a remote area of Yemen. The affected children presented with prominent palmoplantar keratosis and early periodontitis with only a few remaining teeth. The severity of skin lesions in all patients exhibited seasonal variations. Based on their clinical findings, a diagnosis of PLS was made. Dentists have a significant role in the early diagnosis and management of PLS patients.
- Published
- 2017
13. Prolonged pharmacological inhibition of cathepsin C results in elimination of neutrophil serine proteases
- Author
-
Erhan Firatli, Cécile Croix, Sandrine Dallet-Choisy, Niels Borregaard, Marshall S. Horwitz, John Pedersen, Brice Korkmaz, Marie-Claude Viaud-Massuard, Nathalie Heuzé-Vourc'h, Francis Gauthier, Conni Lauritzen, Sylvain Marchand-Adam, Anne Sophie Lamort, Yveline Hamon, Thomas Baranek, Carla Guarino, Mustapha Si-Tahar, Adam Lesner, and Dieter E. Jenne
- Subjects
0301 basic medicine ,Proteases ,Neutrophils ,medicine.medical_treatment ,Biology ,Cysteine Proteinase Inhibitors ,Biochemistry ,Cathepsin C ,Serine ,03 medical and health sciences ,0302 clinical medicine ,Papillon-Lefevre Disease ,Proteinase 3 ,medicine ,Animals ,Humans ,Pharmacology ,Serine protease ,Protease ,Elastase ,Cysteine protease ,3. Good health ,Macaca fascicularis ,030104 developmental biology ,030220 oncology & carcinogenesis ,Case-Control Studies ,biology.protein ,Female ,Serine Proteases ,Leukocyte Elastase ,Bronchoalveolar Lavage Fluid - Abstract
Cathepsin C (CatC) is a tetrameric cysteine dipeptidyl aminopeptidase that plays a key role in activation of pro-inflammatory serine protease zymogens by removal of a N-terminal pro-dipeptide sequence. Loss of function mutations in the CatC gene is associated with lack of immune cell serine protease activities and cause Papillon-Lefevre syndrome (PLS). Also, only very low levels of elastase-like protease zymogens are detected by proteome analysis of neutrophils from PLS patients. Thus, CatC inhibitors represent new alternatives for the treatment of neutrophil protease-driven inflammatory or autoimmune diseases. We aimed to experimentally inactivate and lower neutrophil elastase-like proteases by pharmacological blocking of CatC-dependent maturation in cell-based assays and in vivo. Isolated, immature bone marrow cells from healthy donors pulse-chased in the presence of a new cell permeable cyclopropyl nitrile CatC inhibitor almost totally lack elastase. We confirmed the elimination of neutrophil elastase-like proteases by prolonged inhibition of CatC in a non-human primate. We also showed that neutrophils lacking elastase-like protease activities were still recruited to inflammatory sites. These preclinical results demonstrate that the disappearance of neutrophil elastase-like proteases as observed in PLS patients can be achieved by pharmacological inhibition of bone marrow CatC. Such a transitory inhibition of CatC might thus help to rebalance the protease load during chronic inflammatory diseases, which opens new perspectives for therapeutic applications in humans.
- Published
- 2017
14. Systemic lupus erythematosus complicated with liver cirrhosis in a patient with Papillon-Lefèvre syndrome
- Author
-
H Takehara, Tsuyoshi Isojima, Yutaka Harita, Tomoaki Ando, Junko Takita, Masato Takeuchi, T Itonaga, Akira Oka, Kenichiro Miura, Hajime Nakano, and Hiroki Yasudo
- Subjects
Liver Cirrhosis ,medicine.medical_specialty ,Cirrhosis ,business.industry ,Papillon–Lefèvre syndrome ,Gene mutation ,medicine.disease ,Dermatology ,Cathepsin C ,Hepatitis, Autoimmune ,Papillon-Lefevre Disease ,Rheumatology ,Immunology ,Humans ,Lupus Erythematosus, Systemic ,Medicine ,Female ,In patient ,Child ,business ,Complication ,Anti-SSA/Ro autoantibodies - Abstract
We report the first case of a girl who presented with Papillon-Lefèvre syndrome (PLS) and subsequently developed systemic lupus erythematosus and liver cirrhosis. This indicates that autoimmune diseases can be a complication in patients with PLS. Cathepsin C gene mutations were not found in our patient or her mother. Thus, other genetic factors may have been involved in this patient.
- Published
- 2014
15. [Papillon-Lefèvre syndrome: A new case]
- Author
-
S, Martinho, T, Levade, P, Fergelot, and J-L, Stephan
- Subjects
Patient Care Team ,Delayed Diagnosis ,Genetic Carrier Screening ,DNA Mutational Analysis ,Exons ,Prognosis ,Combined Modality Therapy ,Cathepsin C ,Papillon-Lefevre Disease ,Phenotype ,Child, Preschool ,Humans ,Female ,Interdisciplinary Communication ,Intersectoral Collaboration - Abstract
Papillon-Lefèvre syndrome (PLS) is a rare primary immunodeficiency, which combines severe periodontal disease with edentulism and palmoplantar keratosis (PPK). PLS is inherited as an autosomal recessive trait and is due to mutations in the cathepsin C gene. The biological properties of the neutrophils (PN) are altered, leading to a gingival dysbiosis and bacterial overgrowth, with intense inflammation of the periodontium. We report the observation of a 4-year-old girl who presented to the clinic with gingivitis, partial edentulism, and PPK, whose diagnosis, raised after a long delay, was suggested by null cathepsin C activity and confirmed by the presence of heterozygous mutations in exon 4: c.628CT, pArg210* and in exon 7: c.1286GA, p.Trp429*. A multidisciplinary approach transformed the functional and esthetic prognosis and psychological behavior of this child. This classical observation describes this poorly known phenotype.
- Published
- 2016
16. [Screening of CTSC gene mutations in a Chinese pedigree affected with Papillon-Lefevre syndrome]
- Author
-
Cuixian, Liu, Zhihui, Tian, Qi, Yang, Qianqian, Ma, Xiangmin, Xu, and Fu, Xiong
- Subjects
Adult ,Male ,China ,Base Sequence ,Molecular Sequence Data ,Exons ,Cathepsin C ,Pedigree ,Papillon-Lefevre Disease ,Asian People ,Child, Preschool ,Mutation ,Humans ,Female - Abstract
To analyze the clinical phenotype of a Chinese pedigree affected with Papillon-Lefevre syndrome(PLS) and detect mutation of CTSC gene.Clinical phenotypes were noted, and oral examination for the proband was carried out for the clinical diagnosis of PLS. PCR and Sanger sequencing were used to identify potential mutation of the CTSC gene. Functional effect of the mutation was predicted with SIFT and PolyPhen-2. Swiss-Port was used to predict the tertiary structure of wild type and mutant proteins. The mRNA and protein expression were analyzed by real-time PCR and Western blotting.A homozygous mutation c.901GA (p.G301S) in exon 7 of CTSC gene was identified in the patient. Both parents of the patient had carried a heterozygous c.901GA mutation. The mutation was located in the conserved region of CTSC enzyme and was predicted to be damaging by changing the structure of the protein, which could affect the activity of Cathepsin C. However, no significant difference was found in the expression of p.G301S variant at the mRNA and protein levels compared with that of the wild type CTSC gene.The c.901GA mutation of the CTSC gene was first reported in China, which has expanded its mutation spectrum.
- Published
- 2016
17. Analysis of urinary cathepsin C for diagnosing Papillon-Lefevre syndrome
- Author
-
Maurizio Battino, Adam Lesner, Nikoletta Nagy, Patricia Fergelot, Hadi Kord, Dieter E. Jenne, Elodie Kara, Salih Kavukçu, Celia Moss, Sylvain Marchand-Adam, Brice Korkmaz, Beate Schacher, Peter Eickholz, Alain Taieb, Louise Newell, Antonia Vlahou, Karen L. David, Fanny Morice-Picard, Márta Széll, Lise Vanderlynden, S Ragunatha, Charalampos Tsamakis, Francis Gauthier, Cyril Goizet, Yveline Hamon, Ian Surplice, Jerome Zoidakis, Abdullah Al Farraj Aldosari, Sevil Korkmaz-Icöz, Karina Acrich, Monika Legowska, Xinwen Wang, Ali Kord Valeshabad, Yang Liu, Sandrine Dallet-Choisy, Katalin Farkas, Comprehensive Pneumology Center - Institute of Lung Biology and Disease (iLBD), German Center for Lung Research, Université Francois Rabelais [Tours], Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Max Planck Institute of Neurobiology (MPIN), Max-Planck-Gesellschaft, Faculty of Chemistry, Technion - Israel Institute of Technology [Haifa], U1211 Laboratoire Maladies Rares: Génétique et Métabolisme, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Hôpital Pellegrin - Service de Génétique Médicale, CHU Bordeaux [Bordeaux], Centre de Référence des Anomalies du Développement Embryonnaire, Birmingham Children’s Hospital, Department of Physics [Boulder], University of Colorado [Boulder], Medical Genetics Clinic, Metropolitan Hospital Center, Bone Joint and Connective Tissue Disease Research Center (BJCRC), Department of Rheumatology, Faculty of Medicine, Golestan University of Medical Sciences, U1035 Centre de Référence pour les Maladies Rares de la Peau, Service de Dermatologie Adulte et Pédiatrique, Biotechnology Division - Biomedical Research Foundation, Academy of Athens, Department of Dermatology, Venereology, and Leprosy, Sri Siddhartha Medical College, Department of Medical Genetics, University Hospital of North-Norway, Department of Dermatology and Allergology [Szeged], University of Szeged [Szeged], MTA-SZTE Dermatological Research Group, CHU Pitié-Salpêtrière [APHP], Centre for Nutrition & Health, Universidad Europea del Atlantico, Department of Clinical Sciences, Swedish University of Agricultural Sciences (SLU), Department of Prosthetic, College of Dentistry, King Saud University, Department of Oral Medicine and Periodontology, School of Stomatology, Fourth Military Medical University (FMMU), Department of Periodontology, People's Liberation Army No. 309 Hospital, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Department of Cardiac Surgery, University Hospital Schleswig-Holstein-Campus Lübeck, University of Birmingham, U1035 Centre de R ef erence pour les Maladies Rares de la Peau, Service de Dermatologie Adulte et Pédiatrique, Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Dokuz Eylul University, INSERM (ITMO Immunology, Hematology, Pneumology), Alexandre von Humboldt Foundation, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), King Saud University [Riyadh] (KSU), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Adult ,Male ,0301 basic medicine ,Adolescent ,cathepsin C ,Urinary system ,[SDV]Life Sciences [q-bio] ,Urine ,Papillon–Lefèvre syndrome ,Biology ,Biochemistry ,Papillon-Lefevre Disease ,Cathepsin C ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,diagnostic method ,medicine ,Papillon-Lefevre syndrome ,Humans ,Aggressive periodontitis ,Papillon-lefèvre Syndrome ,Diagnostic Method ,Protease ,Urine Analysis ,Child ,Molecular Biology ,Aged ,Aged, 80 and over ,Periodontitis ,urine analysis ,Infant ,protease ,030206 dentistry ,Cell Biology ,Middle Aged ,medicine.disease ,Healthy Volunteers ,3. Good health ,Phenotype ,030104 developmental biology ,Palmoplantar keratoderma ,Child, Preschool ,Immunology ,Female - Abstract
Papillon-Lefevre syndrome (PLS) (OMIM: 245000) is a rare disease characterized by severe periodontitis and palmoplantar keratoderma. It is caused by mutations in both alleles of the cathepsin C (CatC) gene CTSC that completely abrogate the proteolytic activity of this cysteine proteinase. Most often, a genetic analysis to enable early and rapid diagnosis of PLS is unaffordable or unavailable. In this study, we tested the hypothesis that active CatC is constitutively excreted and can be easily traced in the urine of normal subjects. If this is true, determining its absence in the urine of patients would be an early, simple, reliable, low-cost and easy diagnostic technique. All 75 urine samples from healthy control subjects (aged 3 months to 80 years) contained proteolytically active CatC and its proform, as revealed by kinetic analysis and immunochemical detection. Of the urine samples of 31 patients with a PLS phenotype, 29 contained neither proteolytically active CatC nor the CatC antigen, so that the PLS diagnosis was confirmed. CatC was detected in the urine of the other two patients, and genetic analysis revealed no loss-of-function mutation in CTSC, indicating that they suffer from a PLS-like condition but not from PLS. Screening for the absence of urinary CatC activity soon after birth and early treatment before the onset of PLS manifestations will help to prevent aggressive periodontitis and loss of many teeth, and should considerably improve the quality of life of PLS patients.
- Published
- 2016
18. Papillon-Lefevre Syndrome: Prosthodontic Rehabilitation of Oral Function
- Author
-
Ayesha, Aslam, Nida, Ovais, Muhammad Uzair, Riaz, and Bilal, Ahmed
- Subjects
Male ,Tooth Loss ,Papillon-Lefevre Disease ,Treatment Outcome ,Adolescent ,Dental Implantation, Endosseous ,Denture, Partial, Removable ,Humans ,Female ,Mouth, Edentulous ,Periodontal Diseases - Published
- 2015
19. Cytokine production by leukocytes of Papillon–Lefèvre syndrome patients in whole blood cultures
- Author
-
Peter Eickholz, Heiko Mühl, Josef Pfeilschifter, Barbara Noack, Christian D. Sadik, and Beate Schacher
- Subjects
Adult ,Lipopolysaccharides ,Male ,Adolescent ,Neutrophils ,medicine.medical_treatment ,Interleukin-1beta ,Biology ,Cathepsin C ,Proinflammatory cytokine ,Interferon-gamma ,Young Adult ,Adenosine Triphosphate ,Papillon-Lefevre Disease ,Escherichia coli ,Leukocytes ,medicine ,Humans ,Interleukin 8 ,Child ,Interleukin 6 ,General Dentistry ,Whole blood ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Interleukin-8 ,Aggregatibacter actinomycetemcomitans ,Interleukin ,biology.organism_classification ,Chemokine CXCL10 ,Cytokine ,Aggressive Periodontitis ,Mutation ,Immunology ,biology.protein ,Cytokines ,Female ,Inflammation Mediators ,Biomarkers - Abstract
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.
- Published
- 2011
20. Detection of an Intragenic Deletion Expands the Spectrum of CTSC Mutations in Papillon–Lefèvre Syndrome
- Author
-
Cyril Goizet, Emmanuel Delaporte, Isabelle Coupry, Benoit Arveiler, Ingrid Burgelin, Didier Lacombe, Claire Douillard, Thomas Jouary, Thierry Levade, Isabelle Redonnet-Vernhet, Annick Toutain, and Alain Taieb
- Subjects
Adult ,Male ,DNA Mutational Analysis ,Gene Dosage ,Papillon–Lefèvre syndrome ,Dermatology ,Biology ,medicine.disease_cause ,Compound heterozygosity ,Gene dosage ,Biochemistry ,Cathepsin C ,Exon ,Papillon-Lefevre Disease ,medicine ,Missense mutation ,Humans ,Genetic Testing ,Molecular Biology ,Genetics ,Family Health ,Mutation ,Splice site mutation ,Cell Biology ,medicine.disease ,Child, Preschool ,Female ,Gene Deletion - Abstract
The Papillon–Lefèvre syndrome (PLS) is an autosomal recessive disorder. The gene responsible for the disease, cathepsin C (CTSC), is localized in 11q14.1–q14.21. We performed mutational and functional analyses of CTSC in two patients affected by this condition. Three previously unreported CTSC mutations were identified. The first patient had a compound heterozygous status with a p.G386R missense mutation and an intragenic deletion spanning exons 3–7. Second patient carried a homozygous splice site mutation, p.A253SfsX30. CTSC activity was undetectable in both patients, thus demonstrating the pathological effect of these mutations. We describe early evidence of an original intragenic deletion reported in PLS. Since this mutational mechanism could not be detected by direct sequencing, intragenic deletion has to be specifically investigated using gene dosage analysis techniques such as quantitative multiplex fluorescent polymerase chain reaction. We consider that this technique should be performed in patients with apparently homozygous CTSC mutations when one parent does not carry the expected mutation or is not available for analysis.
- Published
- 2008
- Full Text
- View/download PDF
21. Dermatologic, periodontal, and skeletal manifestations of Haim-Munk syndrome in two siblings
- Author
-
Shahbaz A. Janjua, Nadia Iftikhar, Amor Khachemoune, and Ijaz Hussain
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Adolescent ,Haim–Munk syndrome ,Hyperkeratosis ,Dermatology ,Papillon–Lefèvre syndrome ,Cathepsin C ,Consanguinity ,Arachnodactyly ,Papillon-Lefevre Disease ,Keratoderma, Palmoplantar ,medicine ,Humans ,Onychogryphosis ,Periodontal Diseases ,Bone Diseases, Developmental ,business.industry ,Syndrome ,medicine.disease ,Dyskeratosis ,Palmoplantar keratoderma ,Female ,business - Abstract
Haim-Munk syndrome is an extremely rare autosomal recessive disorder of keratinization characterized clinically by palmoplantar hyperkeratosis, severe early onset periodontitis, onychogryphosis, pes planus, arachnodactyly, and acro-osteolysis. Recently, germline mutations in the lysosomal protease cathepsin C gene have been identified as the underlying genetic defect in Haim-Munk syndrome and in the clinically related disorders, Papillon-Lefèvre syndrome and prepubertal periodontitis.
- Published
- 2008
22. Aggressive periodontitis associated with Papillon-Lefèvre syndrome: Report of a 14-year follow-up
- Author
-
Raquel Assed Bezerra da Silva, Sada Assed, Léa Assed Bezerra da Silva, and Aldevina Campos de Freitas
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,Dentistry ,Aggregatibacter actinomycetemcomitans ,Oral hygiene ,Papillon-Lefevre Disease ,Scaling and root planing ,medicine ,Tooth loss ,Humans ,Aggressive periodontitis ,Periodontal Debridement ,Child ,Periodontitis ,General Dentistry ,Denture, Complete ,business.industry ,medicine.disease ,Antibiotic coverage ,Surgery ,Treatment Outcome ,Dental Care for Chronically Ill ,Tooth Extraction ,Female ,Tooth Mobility ,Dentures ,medicine.symptom ,business ,Follow-Up Studies - Abstract
This case report describes the periodontal management, therapeutic approach, and 14-year follow-up of a patient diagnosed with Papillon-Lefevre syndrome (PLS). A female child, diagnosed with PLS-associated periodontitis at the age of 9 years and 11 months, presented with hyperkeratosis of the palms and soles, as well as generalized aggressive periodontitis. The dental treatment comprised standard periodontal debridement, scaling and root planing, instructions on oral hygiene, restorations, extraction of hopelessly affected teeth and a therapeutic use of antibiotics. The concomitant supportive periodontal therapy and antibiotic coverage could not stop the loss of periodontal attachment and destruction of the alveolar bone. Four years after treatment was initiated, the last remaining teeth were extracted and complete dentures were constructed. The dentures have been periodically replaced and the patient continues to return for follow-up once a year. The combination of intensive periodontal treatment and antibiotic regimen only temporarily delayed periodontal disease progression and did not prevent loss of both primary and permanent teeth. The outcome of this long-term follow-up case report shows that management of PLS-associated periodontitis is further complicated when the patient is first seen in the mixed dentition stage or later. In these situations, the chances of controlling the progression of periodontal breakdown and minimizing tooth loss are greatly reduced.
- Published
- 2007
23. Papillon-Lefevre syndrome: Two case reports
- Author
-
Jigna S Shah and Shweta Goel
- Subjects
Male ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,Adolescent ,Alveolar Bone Loss ,Dentistry ,Papillon–Lefèvre syndrome ,Tooth Exfoliation ,Severe periodontitis ,precocious loss of the dentition ,Papillon-Lefevre Disease ,medicine ,Papillon-Lefevre syndrome ,Humans ,Periodontitis ,skin and connective tissue diseases ,General Dentistry ,Permanent teeth ,Palmoplantar hyperkeratosis ,business.industry ,General Medicine ,medicine.disease ,Dermatology ,Gingivitis ,lcsh:RK1-715 ,stomatognathic diseases ,Palmoplantar keratoderma ,lcsh:Dentistry ,Female ,business - Abstract
Papillon-Lefevre syndrome is a rare autosomal recessive disorder in which there is palmoplantar keratinization and premature loss of both deciduous and permanent teeth. The palmoplantar keratoderma typically has its onset between the ages of 1 and 4 years and severe periodontitis starts at the age of 3 or 4 years. An early diagnosis of the syndrome can help preserve the teeth by early institution of treatment, using a multidisciplinary approach. We present two cases of the syndrome having all of the characteristic features.
- Published
- 2007
24. Characterization of neutrophil function in Papillon-Lefèvre syndrome
- Author
-
Helen Roberts, Irundika H.K. Dias, Ratna Veeramachaneni, Iain L. C. Chapple, Phillipa White, Sarah J. McKaig, Melissa M. Grant, and Nalin Thakker
- Subjects
0301 basic medicine ,Adult ,Male ,Adolescent ,Neutrophils ,Immunology ,Papillon–Lefèvre syndrome ,Biology ,Extracellular Traps ,Proinflammatory cytokine ,Cathepsin C ,03 medical and health sciences ,Young Adult ,Papillon-Lefevre Disease ,Extracellular ,medicine ,Immunology and Allergy ,Humans ,Child ,Periodontitis ,chemistry.chemical_classification ,Reactive oxygen species ,Chemotaxis ,Cell Biology ,Neutrophil extracellular traps ,medicine.disease ,Chemotaxis, Leukocyte ,030104 developmental biology ,chemistry ,Case-Control Studies ,Cytokines ,Female ,Reactive Oxygen Species - Abstract
Papillon-Lefévre syndrome is a rare, inherited, autosomal-recessive disease, characterized by palmoplantar keratosis and severe prepubertal periodontitis, leading to premature loss of all teeth. Papillon-Lefévre syndrome is caused by a mutation in the cathepsin C gene, resulting in complete loss of activity and subsequent failure to activate immune response proteins. Periodontitis in Papillon-Lefévre syndrome is thought to arise from failure to eliminate periodontal pathogens as a result of cathepsin C deficiency, although mechanistic pathways remain to be elucidated. The aim of this study was to characterize comprehensively neutrophil function in Papillon-Lefévre syndrome. Peripheral blood neutrophils were isolated from 5 patients with Papillon-Lefévre syndrome, alongside matched healthy control subjects. For directional chemotactic accuracy, neutrophils were exposed to the chemoattractants MIP-1α and fMLP and tracked by real-time videomicroscopy. Reactive oxygen species generation was measured by chemiluminescence. Neutrophil extracellular trap formation was assayed fluorometrically, and proinflammatory cytokine release was measured following overnight culture of neutrophils with relevant stimuli. Neutrophil serine protease deficiencies resulted in a reduced ability of neutrophils to chemotax efficiently and an inability to generate neutrophil extracellular traps. Neutrophil extracellular trap-bound proteins were also absent in Papillon-Lefévre syndrome, and Papillon-Lefévre syndrome neutrophils released higher levels of proinflammatory cytokines in unstimulated and stimulated conditions, and plasma cytokines were elevated. Notably, neutrophil chemoattractants MIP-1α and CXCL8 were elevated in Papillon-Lefévre syndrome neutrophils, as was reactive oxygen species formation. We propose that relentless recruitment and accumulation of hyperactive/reactive neutrophils (cytokines, reactive oxygen species) with increased tissue transit times into periodontal tissues, alongside a reduced antimicrobial capacity, create a locally destructive chronic inflammatory cycle in Papillon-Lefévre syndrome.
- Published
- 2015
25. Role of polymorphonuclear leukocyte-derived serine proteinases in defense against Actinobacillus actinomycetemcomitans
- Author
-
Vincent Everts, Martijn T. J. M. van Steenbergen, Pieter S. Hiemstra, Susanne F de Haar, Wouter Beertsen, Orale Celbiologie (OUD, ACTA), MKA (OUD, ACTA), and Parodontologie (OUD, ACTA)
- Subjects
Adult ,Male ,Proteases ,Neutrophils ,Immunology ,Exotoxins ,Biology ,Cathepsin G ,Microbiology ,Aggregatibacter actinomycetemcomitans ,Cathepsin C ,Serine ,chemistry.chemical_compound ,Actinobacillus Infections ,Papillon-Lefevre Disease ,Proteinase 3 ,Cathelicidins ,Humans ,Pathogen ,Host Response and Inflammation ,Elastase ,Serine Endopeptidases ,biology.organism_classification ,Infectious Diseases ,chemistry ,Actinobacillus ,Parasitology ,Female ,Antimicrobial Cationic Peptides - Abstract
Periodontitis is a chronic destructive infection of the tooth-supportive tissues, which is caused by pathogenic bacteria such asActinobacillus actinomycetemcomitans. A severe form of periodontitis is found in Papillon-Lefèvre syndrome (PLS), an inheritable disease caused by loss-of-function mutations in the cathepsin C gene. Recently, we demonstrated that these patients lack the activity of the polymorphonuclear leukocyte (PMN)-derived serine proteinases elastase, cathepsin G, and proteinase 3. In the present study we identified possible pathways along which serine proteinases may be involved in the defense againstA. actinomycetemcomitans. Serine proteinases are capable to convert the PMN-derived hCAP-18 into LL-37, an antimicrobial peptide with activity againstA. actinomycetemcomitans. We found that the PMNs of PLS patients released lower levels of LL-37. Furthermore, because of their deficiency in serine proteases, the PMNs of PLS patients were incapable of neutralizing the leukotoxin produced by this pathogen, which resulted in increased cell damage. Finally, the capacity of PMNs from PLS patients to killA. actinomycetemcomitansin an anaerobic environment, such as that found in the periodontal pocket, seemed to be reduced. Our report demonstrates a mechanism that suggests a direct link between an inheritable defect in PMN functioning and difficulty in coping with a periodontitis-associated pathogen.
- Published
- 2006
26. [Recurrent European missense mutation in a Hungarian pedigree with Papillon-Lefèvre syndrome]
- Author
-
Péter, Vályi, Katalin, Farkas, Kornélia, Tripolszki, Adrienn, Sulák, Márta, Széll, Nikoletta, Nagy, and Katalin, Nagy
- Subjects
Adult ,Europe ,Hungary ,Papillon-Lefevre Disease ,Aggressive Periodontitis ,Mutation, Missense ,Humans ,Female ,Sequence Analysis, DNA ,Mouth, Edentulous ,Cathepsin C ,Pedigree - Abstract
Papillon-Lefèvre syndrome, a rare disease with autosomal recessive inheritance, is characterized by aggressive periodontitis and palmoplantar hyperkeratosis. Mutations of the cathepsin C gene are responsible for the development of the disease. In this study, we aimed to describe in details the clinical symptoms and to determine the underlying genetic abnormality in two Hungarian siblings affected by Papillon-Lefèvre syndrome. The siblings are under regular dental and dermatological care since their symptoms appeared, but, due to the fact that genetic analysis of Papillon-Lefèvre syndrome has been available for one or two years in Hungary, their mutation screenings were just recently performed. We have identified a homozygous missense mutation on the cathepsin C gene, which is an already published mutation and was originally reported from Germany. Our investigations would like to draw attention to a rare disease, Papillon-Lefèvre syndrome, in which first symptom can be the aggressive periodontitis, and in which genetic testing and for helping child-bearing and family planning is now available.
- Published
- 2014
27. Clinical, Genetic, and Biochemical Findings in Two Siblings With Papillon-Lefèvre Syndrome
- Author
-
Alparslan Gokalp, Sema S. Hakki, Thomas C. Hart, Ok Hee Ryu, Recep Dursun, P. Suzanne Hart, Hatice Toy, and N. Arzu Cagli
- Subjects
Cathepsin G ,Guanine ,Genes, Recessive ,Papillon–Lefèvre syndrome ,Disease ,Biology ,Gene mutation ,Severe periodontitis ,Cathepsin C ,Root Planing ,chemistry.chemical_compound ,Papillon-Lefevre Disease ,Scaling and root planing ,Anti-Infective Agents ,Metronidazole ,medicine ,Humans ,Child ,Periodontitis ,Adenine ,Chlorhexidine ,Serine Endopeptidases ,Amoxicillin ,medicine.disease ,Cathepsins ,Anti-Bacterial Agents ,Drug Combinations ,chemistry ,Child, Preschool ,Mutation ,Immunology ,Anti-Infective Agents, Local ,Dental Scaling ,Periodontics ,Female ,Leukocyte Elastase - Abstract
Papillon-Lefèvre Syndrome (PLS) is an autosomal recessive disease characterized by palmoplantar hyperkeratosis and severe periodontitis affecting both primary and secondary dentitions. Cathepsin C (CTSC) gene mutations are etiologic for PLS. The resultant loss of CTSC function is responsible for the severe periodontal destruction seen clinically.A 4-year-old female (case 1) and her 10-year-old sister (case 2) presented with palmoplantar skin lesions, tooth mobility, and advanced periodontitis. Based on clinical findings, the cases were diagnosed with PLS. Mutational screening of the CTSC gene was conducted for the cases, and their clinically unaffected parents and brother. Biochemical analysis was performed for CTSC, cathepsin G (CTSG), and elastase activity in neutrophils for all members of the nuclear family. The initial treatment included oral hygiene instruction, scaling and root planing, and systemic amoxicillin-metronidazole therapy.CTSC mutational screening identified a c.415GA transition mutation. In the homozygous state, this mutation was associated with an almost complete loss of activity of CTSC, CTSG, and elastase. Although monthly visits, including scaling, polishing, and 0.2% chlorhexidine digluconate irrigation were performed to stabilize the periodontal condition, case 1 lost all her primary teeth. In case 2, some of the permanent teeth could be maintained.This report describes two siblings with a cathepsin C gene mutation that is associated with the inactivity of cathepsin C and several neutrophil serine proteases. The failure of patients to respond to periodontal treatment is discussed in the context of these biological findings.
- Published
- 2005
28. Impaired Cytotoxicity in Papillon-Lefèvre Syndrome
- Author
-
R S Parhar, Stefan Renvert, Tord Lundgren, and D N Tatakis
- Subjects
Adult ,Cytotoxicity, Immunologic ,Male ,0301 basic medicine ,Adolescent ,T-Lymphocytes ,Biology ,T-Lymphocytes, Regulatory ,Leukocyte Count ,03 medical and health sciences ,Interleukin 21 ,Papillon-Lefevre Disease ,0302 clinical medicine ,Immune system ,White blood cell ,medicine ,Humans ,Cytotoxic T cell ,Lymphocyte Count ,Child ,Periodontitis ,Cytotoxicity ,General Dentistry ,B-Lymphocytes ,Lymphokine-activated killer cell ,T-Lymphocytes, Helper-Inducer ,030206 dentistry ,Flow Cytometry ,Natural killer T cell ,Chromium Radioisotopes ,Killer Cells, Natural ,030104 developmental biology ,medicine.anatomical_structure ,Child, Preschool ,Peripheral blood lymphocyte ,Immunology ,Female ,Radiopharmaceuticals ,K562 Cells - Abstract
Papillon-Lefèvre syndrome (PLS), palmoplantar hyperkeratosis with periodontitis, has been genetically characterized. However, suspected associated immune dysfunctions remain elusive. The purpose of this study was to evaluate peripheral blood lymphocyte levels and natural killer (NK) cell cytotoxicity in PLS. Twenty patients and 20 healthy controls were examined. Peripheral blood lymphocytes were analyzed by flow cytometry for surface markers. NK cell cytotoxicity against K562 cells was determined by means of a51Cr release assay. White blood cell differential and proportions of B-, T-, T-helper, T-suppressor, and NK cells revealed only sporadic borderline variations from control values. In contrast, NK cell cytotoxicity was consistently and severely depressed (32–53% of control values) in all patients. To the best of our knowledge, this newly described impairment of NK cell cytotoxic function is the first consistent immune dysfunction reported in PLS. This suggests that the impaired NK cell cytotoxicity might contribute to the pathogenesis of PLS-associated periodontitis.
- Published
- 2005
29. Complete homozygous deletion ofCTSCin an Iranian family with Papillon-Lefèvre syndrome
- Author
-
Uwe Eckelt, Samira Basir Shabestari, Farzaneh Agha-Hosseini, Barbara Noack, Maria Jatzwauk, Parvin Mehdipour, Hans K. Schackert, Stephanie von Kannen, Per Hoffmann, and Heike Görgens
- Subjects
Adult ,Male ,Genetics ,Base Sequence ,business.industry ,Chromosomes, Human, Pair 11 ,DNA Mutational Analysis ,Homozygote ,Dermatology ,Papillon–Lefèvre syndrome ,Iran ,medicine.disease ,Papillon-Lefevre Disease ,Cathepsin C ,Pedigree ,Young Adult ,Humans ,Medicine ,Female ,Base sequence ,business ,Sequence Deletion - Published
- 2013
30. A novel seven-base deletion of the CTSC gene identified in a Hungarian family with Papillon-Lefèvre syndrome
- Author
-
Ferenc Papp, Lajos Kemény, Márta Széll, Ekaterine Paschali, Katalin Farkas, Zsanett Csoma, Péter Vályi, and Nikoletta Nagy
- Subjects
Male ,Heterozygote ,Heredity ,Adolescent ,DNA Mutational Analysis ,Dermatology ,Papillon–Lefèvre syndrome ,Biology ,medicine.disease_cause ,Cathepsin C ,Frameshift mutation ,Tooth Loss ,Exon ,Papillon-Lefevre Disease ,medicine ,Humans ,Coding region ,Genetic Predisposition to Disease ,Child ,Gene ,Sequence Deletion ,Skin ,Genetics ,Hungary ,Mutation ,Homozygote ,General Medicine ,medicine.disease ,Molecular biology ,Stop codon ,Pedigree ,Phenotype ,Child, Preschool ,Female - Abstract
Papillon-Lefévre syndrome (PLS; OMIM 245000) is a rare autosomal recessive condition characterized by symmetrical palmoplantar hyperkeratosis and periodontal inflammation, causing loss of both the deciduous and permanent teeth. PLS develops due to mutations in the cathepsin C gene, CTSC. Recently we have identified a Hungarian PLS family with two affected siblings. Direct sequencing of the coding regions of the CTSC gene revealed a novel seven-base deletion leading to frameshift and early stop codon in the fourth exon of the CTSC gene (c.681delCATACAT, p.T188fsX199). The affected family members carried the mutation in homozygous form, while the clinically unaffected family members carried the mutation in heterozygous form. The unrelated controls carried only the wild type sequence. In this paper we report a novel homozygous deletion of seven bases on the CTSC gene leading to the development of PLS. Since consanguineous marriage was unknown in the investigated family, the presence of the homozygous seven-base deletion of the CTSC gene may suggest that the parents are close relatives.
- Published
- 2013
31. Papillon-Lefèvre Syndrome: Correlating the Molecular, Cellular, and Clinical Consequences of Cathepsin C/Dipeptidyl Peptidase I Deficiency in Humans
- Author
-
Christine T.N. Pham, Sofia Z. Raptis, Jennifer Ivanovich, Barbara Zehnbauer, and Timothy J. Ley
- Subjects
Adult ,Male ,Blood Bactericidal Activity ,Proteases ,Cathepsin G ,Adolescent ,Neutrophils ,Myeloblastin ,Immunology ,Mutation, Missense ,Cathepsin C ,Granzymes ,Microbiology ,Serine ,chemistry.chemical_compound ,Papillon-Lefevre Disease ,Humans ,Immunology and Allergy ,Killer Cells, Lymphokine-Activated ,Cells, Cultured ,Serine protease ,biology ,Genetic Carrier Screening ,Serine Endopeptidases ,Cytotoxicity Tests, Immunologic ,Cathepsins ,Cysteine protease ,Enzyme Activation ,Biochemistry ,chemistry ,Granzyme ,Neutrophil elastase ,biology.protein ,Female ,Leukocyte Elastase - Abstract
A variety of neutral serine proteases are important for the effector functions of immune cells. The neutrophil-derived serine proteases cathepsin G and neutrophil elastase are implicated in the host defense against invading bacterial and fungal pathogens. Likewise, the cytotoxic lymphocyte and NK cell granule-associated granzymes A and B are important for the elimination of virus-infected cells. The activation of many of these serine proteases depends on the N-terminal processing activity of the lysosomal cysteine protease cathepsin C/dipeptidyl peptidase I (DPPI). Although mice deficient in DPPI have defects in serine protease activation in multiple cellular compartments, the role of DPPI for human serine protease activation is largely undefined. Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disease associated with loss-of-function mutations in the DPPI gene locus. In this study, we established that the loss of DPPI activity is associated with severe reduction in the activity and stability of neutrophil-derived serine proteases. Surprisingly, patients with PLS retain significant granzyme activities in a cytotoxic lymphocyte compartment (lymphokine-activated killer) and have normal lymphokine-activated killer-mediated cytotoxicity against K562 cells. Neutrophils from patients with PLS do not uniformly have a defect in their ability to kill Staphylococcus aureus and Escherichia coli, suggesting that serine proteases do not represent the major mechanism used by human neutrophils for killing common bacteria. Therefore, this study defines the consequences of DPPI deficiency for the activation of several immune cell serine proteases in humans, and provides a molecular explanation for the lack of a generalized T cell immunodeficiency phenotype in patients with PLS.
- Published
- 2004
32. Lipid Composition of Outer Stratum corneum in Hereditary Palmoplantar Keratodermas
- Author
-
Wolfgang Küster, Henning Hamm, Heiko Traupe, and Bodo C. Melnik
- Subjects
Adult ,Male ,Adolescent ,Hyperkeratosis ,Dermatology ,Fatty Acids, Nonesterified ,Biology ,Ceramides ,Papillon-Lefevre Disease ,Keratoderma, Palmoplantar ,Stratum corneum ,medicine ,Humans ,Child ,Keratoderma ,Chromatography, High Pressure Liquid ,Lipid Biochemistry ,integumentary system ,Lipid metabolism ,Middle Aged ,medicine.disease ,Lipids ,Dyskeratosis ,medicine.anatomical_structure ,Palmoplantar keratoderma ,Biochemistry ,Child, Preschool ,Female ,lipids (amino acids, peptides, and proteins) ,Epidermis - Abstract
Background: The analysis of lipid composition of the outer stratum corneum is a promising approach to study the pathophysiology of inherited disorders of keratinization. Objective: The purpose of the study was the search for biochemical alterations of stratum corneum lipids in hereditary palmoplantar keratoderma (PPK). Methods: Using high-performance thin-layer chromatography, we performed an analysis of all major stratum corneum lipid classes in scales of 29 patients with 8 different types of hereditary PPK. Results: In comparison to the controls, slight differences in the lipid pattern were found in all keratodermas. Reduced amounts of total ceramides and increased levels of free fatty acids were noted in nearly all types. Conclusions: The study indicates that the abnormal composition of stratum corneum lipids in PPK is probably not caused by genetic defects of the epidermal lipid metabolism, but it appears to represent an epiphenomenon of a disturbed cornification.
- Published
- 2003
33. THE PRESENCE OF CYTOKINE (IL-8, IL-1α, IL-1β)-PRODUCING CELLS IN INFLAMED GINGIVAL TISSUE FROM A PATIENT MANIFESTING PAPILLON-LEFEVRE SYNDROME (PLS)
- Author
-
Kazuaki Nonaka, Takao Hirofuji, Hiroaki Kabashima, Katsumasa Maeda, Masahiro Yoneda, and Kengo Nagata
- Subjects
Blood Bactericidal Activity ,Pathology ,medicine.medical_specialty ,Neutrophils ,medicine.medical_treatment ,Phagocytosis ,Immunology ,Gingiva ,Papillon–Lefèvre syndrome ,In Vitro Techniques ,Biochemistry ,Papillon-Lefevre Disease ,Polymorphonuclear Neutrophils ,Humans ,Immunology and Allergy ,Medicine ,Interleukin 8 ,Child ,Molecular Biology ,business.industry ,Gingival tissue ,Interleukin-8 ,Hematology ,medicine.disease ,Immunohistochemistry ,Peripheral blood ,Cytokine ,Aggressive Periodontitis ,Female ,business ,Interleukin-1 - Abstract
The point of this study was to examine the presence or absence of cytokine-positive cells by means of immunohistochemical methods in the samples of inflamed gingival tissues obtained from an 11-year-old girl with Papillon-Lefevre syndrome (PLS). Interleukin-8 (IL-8)-positive cells were found to be present. In addition, IL-1alpha-and IL-1beta-positive cells were detected. No dysfunction in the phagocytosis and the bacterial killing of peripheral blood polymorphonuclear neutrophils (PMNs) was observed in this patient. Our findings suggest that these cytokines may be members responsible for modulating the process of rapidly progressive periodontitis for patient with PLS.
- Published
- 2002
34. Proxy molecular diagnosis from whole-exome sequencing reveals Papillon-Lefevre syndrome caused by a missense mutation in CTSC
- Author
-
A Mesut, Erzurumluoglu, Muslim M, Alsaadi, Santiago, Rodriguez, Tahani S, Alotaibi, Philip A I, Guthrie, Sian, Lewis, Aasiya, Ginwalla, Tom R, Gaunt, Khalid K, Alharbi, Fahad M, Alsaif, Basma M, Alsaadi, and Ian N M, Day
- Subjects
Male ,Consanguinity ,Papillon-Lefevre Disease ,Mutation, Missense ,Saudi Arabia ,Humans ,Exome ,Female ,Sequence Analysis, DNA ,Cathepsin C ,Arabs ,Pedigree ,Research Article - Abstract
Papillon-Lefevre syndrome (PLS) is an autosomal recessive disorder characterised by severe early onset periodontitis and palmoplantar hyperkeratosis. A previously reported missense mutation in the CTSC gene (NM_001814.4:c.899G>A:p.(G300D)) was identified in a homozygous state in two siblings diagnosed with PLS in a consanguineous family of Arabic ancestry. The variant was initially identified in a heterozygous state in a PLS unaffected sibling whose whole exome had been sequenced as part of a previous Primary ciliary dyskinesia study. Using this information, a proxy molecular diagnosis was made on the PLS affected siblings after consent was given to study this second disorder found to be segregating within the family. The prevalence of the mutation was then assayed in the local population using a representative sample of 256 unrelated individuals. The variant was absent in all subjects indicating that the variant is rare in Saudi Arabia. This family study illustrates how whole-exome sequencing can generate findings and inferences beyond its primary goal.
- Published
- 2014
35. Papillon-Lefèvre syndrome patient reveals species-dependent requirements for neutrophil defenses
- Author
-
Finn Cilius Nielsen, Sara Louise Dahl, Niels Borregaard, Andreas Glenthøj, Niels H. H. Heegaard, Ole E. Sørensen, Ole Østergaard, and Stine N. Clemmensen
- Subjects
Adult ,Proteases ,Proteome ,Neutrophils ,Mutation, Missense ,Cell Separation ,Cathepsin G ,Biology ,Defensins/metabolism ,Cathepsin C ,Azurophilic granule ,chemistry.chemical_compound ,Papillon-Lefevre Disease ,Proteinase 3 ,Reactive Oxygen Species/metabolism ,Subcellular Fractions/metabolism ,Humans ,Papillon-Lefevre Disease/genetics ,Serine Proteases/metabolism ,Cathepsin C/genetics ,Antimicrobial Cationic Peptides/metabolism ,Bone Marrow/metabolism ,Elastase ,Homozygote ,Ionomycin/pharmacology ,Neutrophils/cytology ,General Medicine ,Neutrophil extracellular traps ,Flow Cytometry ,Molecular biology ,Cysteine protease ,chemistry ,Immune System ,Female ,Research Article - Abstract
Papillon-Lefevre 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. 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 afect 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.
- Published
- 2014
36. Proteases, neutrophils, and periodontitis: the NET effect
- Author
-
William M. Nauseef
- Subjects
Adult ,Proteases ,Proteome ,Neutrophils ,Phagocytosis ,Mutation, Missense ,Cell Separation ,Biology ,Cathepsin C ,Microbiology ,Serine ,Defensins ,Papillon-Lefevre Disease ,Bone Marrow ,Cathelicidins ,Humans ,Phagosome ,Serine protease ,Ionomycin ,Elastase ,Homozygote ,General Medicine ,Neutrophil extracellular traps ,Flow Cytometry ,Immune System ,biology.protein ,Commentary ,Female ,Serine Proteases ,Reactive Oxygen Species ,Antimicrobial Cationic Peptides ,Subcellular Fractions - Abstract
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.
- Published
- 2014
37. Long-term change of disease behavior in Papillon-Lefèvre syndrome: seven years follow-up
- Author
-
Yang Liu, Qingtao Wang, Zhi-wei Ma, Yuan Liu, Guangying Dong, Qing Liu, Xinwen Wang, and E. Barrie Kenney
- Subjects
Male ,medicine.medical_specialty ,Adolescent ,Papillon–Lefèvre syndrome ,Disease ,Immunoglobulin E ,Gastroenterology ,Severe periodontitis ,Serum ige ,Cathepsin C ,Tooth Loss ,Young Adult ,Papillon-Lefevre Disease ,Internal medicine ,Genetics ,medicine ,Humans ,Tooth, Deciduous ,Genetics (clinical) ,Palmoplantar hyperkeratosis ,biology ,business.industry ,General Medicine ,medicine.disease ,Immunoglobulin A ,Immunoglobulin G ,Mutation ,biology.protein ,Female ,sense organs ,Antibody ,business ,Follow-Up Studies - Abstract
Papillon-Lefevre syndrome (PLS) is an autosomal recessive disease, characterized by severe periodontitis and palmoplantar hyperkeratosis. Mutations in the cathepsin C (CTSC) gene are the causative genetic factor. PLS starts at very early age, however, the age associated change of PLS has never been characterized. In this report, four PLS patients with CTSC mutations were followed up for seven years, periodontal condition and serum immunoglobulins (Igs) were recorded. Results showed that periodontal inflammation of PLS peaked at teenage years, but declined with time. At the same time the serum IgE change was consistent with the change, suggesting the possibility of using IgE as a monitoring index for PLS inflammation level, or to develop new target for therapy.
- Published
- 2014
38. Palmoplantar keratoderma with progressive gingivitis and recurrent pyodermas
- Author
-
Tyler A, Moss, Anne P, Spillane, Sam F, Almquist, Patrick E, McCleskey, and Oliver J, Wisco
- Subjects
Adult ,Papillon-Lefevre Disease ,Pyoderma ,Recurrence ,Mutation ,Disease Progression ,Humans ,Female ,Gingivitis ,Cathepsin C - Abstract
Papillon-Lefèvre syndrome (PLS) is a rare inherited palmoplantar keratoderma (PPK) that is associated with progressive gingivitis and recurrent pyodermas. We present a case exhibiting classic features of this autosomal-recessive condition and review the current understanding of its pathophysiology, diagnosis, and treatment. Additionally, a review of pertinent transgredient PPKs is undertaken, with key and distinguishing features of each syndrome highlighted.
- Published
- 2014
39. Elevated Hydroperoxide Levels and Antioxidant Patterns in Papillon-Lefèvre Syndrome
- Author
-
Pedro Bullón, Fabrizio Mosca, Stefano Bompadre, Maurizio Battino, Luciana Leone, and Maria-Soledad Ferreiro
- Subjects
Adult ,Male ,Vitamin ,Lipid Peroxides ,Antioxidant ,Ubiquinone ,medicine.medical_treatment ,High-performance liquid chromatography ,Antioxidants ,chemistry.chemical_compound ,Papillon-Lefevre Disease ,medicine ,Humans ,Vitamin E ,chemistry.chemical_classification ,Reactive oxygen species ,General Engineering ,Glutathione ,Pedigree ,Peroxides ,Uric Acid ,Oxidative Stress ,chemistry ,Biochemistry ,Child, Preschool ,Coenzyme Q – cytochrome c reductase ,Periodontics ,Uric acid ,Female - Abstract
Since it has been found that reactive oxygen species seem to be involved in the pathogenesis of both periodontitis and hyperkeratotic syndromes, we studied a group of patients belonging to 3 generations of a family with different degrees of severity of Papillon-Lefèvre syndrome (PLS) to ascertain whether altered concentrations of the most important hydrophobic and hydrophilic plasma antioxidants as well as products of oxidative damage are present in PLS.Coenzyme Q (CoQ), vitamin E, glutathione (GSH), and uric acid were evaluated by high-performance liquid chromatography (HPLC) (supplied with electrochemical detector) techniques and hydroperoxides by a spectrophotometric method.GSH and uric acid were in the range of reference values; CoQ was very low in both the child of the third generation and his mother, and these 2 subjects had the highest hydroperoxide levels. The child also had extremely low values of vitamin E. In general, all family members showed abnormally high hydroperoxide levels, with the exception of those members who are phenotypically healthy.Since the subjects with the lowest hydroperoxide contents are phenotypically healthy, whereas the affected individuals presented lower antioxidant levels and very high hydroperoxide concentrations, it has been suggested that a specific antioxidant therapy could be a promising approach in treating some PLS subjects. Moreover, unexpected manifestations of heterozygosity in the child of the third generation were also detected.
- Published
- 2001
40. Papillon–Lefèvre Syndrome: Mutations and Polymorphisms in the Cathepsin C Gene
- Author
-
Kazuo Nomura, Yoshio Ono, Sal LaForgia, Aoi Nakano, Jouni Uitto, Leena Pulkkinen, Hajime Nakano, and Isao Hashimoto
- Subjects
Heterozygote ,keratoderma ,Mutation, Missense ,Papillon–Lefèvre syndrome ,Dermatology ,Gene mutation ,Biology ,Biochemistry ,Cathepsin C ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Papillon-Lefevre Disease ,Genotype ,medicine ,Missense mutation ,Humans ,Point Mutation ,periodontitis ,Gene ,Molecular Biology ,030304 developmental biology ,Genetics ,Family Health ,0303 health sciences ,Polymorphism, Genetic ,Homozygote ,Genodermatosis ,030206 dentistry ,Cell Biology ,Middle Aged ,medicine.disease ,3. Good health ,Pedigree ,genodermatoses ,Female - Abstract
The Papillon–Lefèvre syndrome, inherited in an autosomal recessive pattern, manifests with palmoplantar keratoderma and early, destructive periodontitis. Recently, mutations in the gene encoding cathepsin C have been disclosed in a limited number of families with Papillon–Lefèvre syndrome. We have examined two multiplex families with Papillon–Lefèvre syndrome, and evaluated the gene encoding cathepsin C for mutations. The mutation detection strategy consisted of polymerase chain reaction amplification of all seven exons and flanking intronic sequences, followed by direct nucleotide sequencing. This strategy identified two missense mutations, W39S and G301S, affecting highly conserved amino acid residues within the cathepsin C polypeptide. The affected individuals were homozygotes whereas heterozygous carriers of the mutations were clinically unaffected, confirming the recessive nature of the mutations. Addition of these cathepsin C gene mutations into the expanding Papillon–Lefèvre syndrome mutation database allows further development of genotype/phenotype correlations towards understanding this severe genodermatosis.
- Published
- 2001
- Full Text
- View/download PDF
41. An integrated physical and genetic map of the PLS locus interval on Chromosome 11q14
- Author
-
Erhan Firatli, Stephen J. Walker, Thomas C. Hart, Donald W. Bowden, Peggy Bobby, Scott A. Callison, and Patricia S. Hart
- Subjects
Expressed Sequence Tags ,Family Health ,Male ,Genetics ,Polymorphism, Genetic ,Monophenol Monooxygenase ,Chromosomes, Human, Pair 11 ,DNA Mutational Analysis ,Locus (genetics) ,DNA ,Biology ,Physical Chromosome Mapping ,Gene Expression Regulation, Enzymologic ,Human genetics ,Contig Mapping ,Papillon-Lefevre Disease ,Humans ,Female ,Tissue Distribution ,Chromosomes, Artificial, Yeast ,Microsatellite Repeats ,Sequence Tagged Sites - Published
- 2000
42. Haim-Munk syndrome and Papillon-Lefevre syndrome are allelic mutations in cathepsin C
- Author
-
T C, Hart, P S, Hart, M D, Michalec, Y, Zhang, E, Firatli, T E, Van Dyke, A, Stabholz, A, Zlotogorski, L, Shapira, W A, Soskolne, and A, Zlorogorski
- Subjects
Genetic Markers ,Male ,Genotype ,Haim–Munk syndrome ,Molecular Sequence Data ,Restriction Mapping ,Locus (genetics) ,Papillon–Lefèvre syndrome ,Gene mutation ,Biology ,Cathepsin C ,Exon ,Papillon-Lefevre Disease ,Genetics ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Allele ,Periodontitis ,Alleles ,Genetics (clinical) ,Hyperkeratosis, Epidermolytic ,Base Sequence ,Sequence Homology, Amino Acid ,Haplotype ,Original Articles ,Syndrome ,medicine.disease ,Pedigree ,Radiography ,Mutation ,Commentary ,Female - Abstract
Of the many palmoplantar keratoderma (PPK) conditions, only Papillon-Lefèvre syndrome (PLS) and Haim-Munk syndrome (HMS) are associated with premature periodontal destruction. Although both PLS and HMS share the cardinal features of PPK and severe periodontitis, a number of additional findings are reported in HMS including arachnodactyly, acro-osteolysis, atrophic changes of the nails, and a radiographic deformity of the fingers. While PLS cases have been identified throughout the world, HMS has only been described among descendants of a religious isolate originally from Cochin, India. Parental consanguinity is a characteristic of many cases of both conditions. Although autosomal recessive transmission of PLS is evident, a more "complex" autosomal recessive pattern of inheritance with phenotypic influences from a closely linked modifying locus has been hypothesised for HMS. Recently, mutations of the cathepsin C gene have been identified as the underlying genetic defect in PLS. To determine if a cathepsin C mutation is also responsible for HMS, we sequenced the gene in affected and unaffected subjects from the Cochin isolate in which both the PLS and HMS phenotypes appear. Here we report identification of a mutation of cathepsin C (exon 6, 2127A→ G) that changes a highly conserved amino acid in the cathepsin C peptide. This mutation segregates with HMS in four nuclear families. Additionally, the existence of a shared common haplotype for genetic loci flanking the cathepsin C gene suggests that affected subjects descended from the Cochin isolate are homozygous for a mutation inherited "identical by descent" from a common ancestor. This finding supports simple autosomal recessive inheritance for HMS in these families. We also report a mutation of the same exon 6 CTSC codon (2126C→T) in a Turkish family with classical PLS. These findings provide evidence that PLS and HMS are allelic variants of cathepsin C gene mutations. Keywords: Papillon-Lefèvre syndrome; Haim-Munk syndrome; cathepsin C mutation; allelic mutations
- Published
- 2000
43. Leukocyte functions in 2 cases of Papillon-Lefèvre syndrome
- Author
-
Zhihui Tang, Caifang Cao, Huanxing Meng, and Rongkun Liu
- Subjects
Adult ,Male ,Neutrophils ,Papillon–Lefèvre syndrome ,Biology ,Lymphocyte Activation ,Monocytes ,Statistics, Nonparametric ,Pathogenesis ,chemistry.chemical_compound ,Papillon-Lefevre Disease ,Polymorphonuclear Neutrophils ,Cell Adhesion ,medicine ,Humans ,Interleukin 8 ,Child ,Periodontitis ,Interleukin-8 ,Elastase ,hemic and immune systems ,Chemotaxis ,Gingival Crevicular Fluid ,medicine.disease ,Peripheral blood ,N-Formylmethionine Leucyl-Phenylalanine ,Chemotaxis, Leukocyte ,Neutrophil Infiltration ,chemistry ,Case-Control Studies ,Immunology ,Periodontics ,Female ,Disease Susceptibility ,Lysozyme ,Leukocyte Elastase - Abstract
Aim: To investigate the role of leukocytes in the pathogenesis of Papillon-Lefevre syndrome (PLS). Methods: Peripheral blood polymorphonuclear neutrophils (PMNs), monocytes (MNs) and gingival crevicular fluid (GCF) were obtained from 2 cases of PLS with typical features. The chemotaxis of PMNs and MNs were evaluated using a modified Boyden chamber. The adherence of PMNs was determined by adherence of PMNs to petri dishes. Interleukin-8 (IL-8) in GCF was detected by sandwich ELISA. Elastase activity in GCF was measured with a low molecular weight substrate (S-2484) specific for granulocyte elastase. Results: PMNs from both patients showed depressed chemotactic response to FMLP and IL-8. Total amounts of IL-8 in GCF from the 2 patients were much higher than those of the normal controls. Elastase activity was not significantly different from that of the controls. The adherence of PMN and the chemotaxis of MN in the 2 patients were normal. Conclusion: The depressed chemotactic response of PMN leads to decreased recruitment of PMN and/or release of lysozyme from PMN in the diseased gingival tissue, increasing the susceptibility of PLS patients to periodontal infection.
- Published
- 2000
44. Late-onset Papillon-Lefevre syndrome with pyogenic liver abscesses: report of one case
- Author
-
Ameneh Yazdanfar and Sasan Farahnaki
- Subjects
Adult ,myalgia ,Abdominal pain ,Time Factors ,Hyperkeratosis ,Acanthosis ,Dermatology ,Iran ,Severity of Illness Index ,Papillon-Lefevre Disease ,medicine ,Humans ,Permanent teeth ,Hypergranulosis ,medicine.diagnostic_test ,business.industry ,Biopsy, Needle ,Anatomy ,Prognosis ,medicine.disease ,Immunohistochemistry ,medicine.anatomical_structure ,Liver Abscess, Pyogenic ,Skin biopsy ,Abdomen ,Female ,medicine.symptom ,Tomography, X-Ray Computed ,business - Abstract
A 25-year-old woman living in Hamedan, Iran, presented originally at 7 years of age with erythematous, hyperkeratotic lesions on the palms and soles with extension to the dorsal side of the hands and feet. Involvement of the elbows and knees was also seen. From 12 years of age, she started to lose her teeth. At the same age, she experienced fever, chills, malaise, myalgia, and right upper quadrant abdominal pain. With a diagnosis of pyogenic liver abscesses, the patient underwent successful surgical treatment. Examination revealed erythematous, hyperkeratotic, scaling plaques on the palms and soles, dorsal side of the hands and feet (Fig. 1), elbows and knees. All the teeth were missing from the mouth (Fig. 2), and she used a dental prosthesis. A surgical scar was observed on the right upper quadrant of the abdomen (Fig. 3). Skull X-ray and computed tomography scan were normal. Skin biopsy of the dorsal right hand demonstrated hyperkeratosis, focal parakeratosis, hypergranulosis, and acanthosis with a mild inflammatory infiltrate around the vessels (Fig. 4). Figure 1. Hyperkeratotic plaques on the hands and feet Download figure to PowerPoint Figure 2. Loss of permanent teeth Download figure to PowerPoint Figure 3. Surgical scar on the right upper quadrant of the abdomen and hyperkeratotic plaques on the hand Download figure to PowerPoint Figure 4. Hyperkeratosis, focal parakeratosis, hypergranulosis, and acanthosis (hematoxylin and eosin, ×40) Download figure to PowerPoint
- Published
- 2009
45. Association of Inflammatory Pseudotumor of the Liver and Papillon-Lefevre Syndrome - Case Report
- Author
-
Andrzej Roszkiewicz, Piotr Czauderna, Maria Korzon, Czeslaw Stoba, and Katarzyna Sznurkowska
- Subjects
Gynecology ,medicine.medical_specialty ,Pathology ,business.industry ,Liver Diseases ,Hyperkeratosis ,Papillon–Lefèvre syndrome ,medicine.disease ,Granuloma, Plasma Cell ,Dyskeratosis ,Papillon-Lefevre Disease ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,medicine ,Humans ,Inflammatory pseudotumor ,Female ,Surgery ,business - Abstract
Un cas de pseudotumeur hepatique de type inflammatoire simulant la malignite est rapporte chez une fille de 4 ans atteinte du syndrome de Papillon-Lefevre (PLS). C'est seulement recemment qu'on a decouvert une association entre ce syndrome hereditaire et des abces du foie. La pathogenie possible est discutee et les deficiences immunologiques resultant du syndrome de Papillon-Lefevre sont rappelees. Le developpement d'une pseudotumeur inflammatoire du foie peut etre cause par des perturbations immunologiques et une surinfection staphylocoecique. Le tableau de tumeur hepatique sur l'imagerie de ces patients avec PLS doit etre plus attribue a une inflammation qu'a un processus neoplasique.
- Published
- 1999
46. Microbiological features of Papillon-Lefèvre syndrome periodontitis
- Author
-
Filomena Salazar, José Pacheco, C. Coelho, Adolfo Contreras, Corsina Velazco, and Jørgen Slots
- Subjects
DNA, Bacterial ,Human cytomegalovirus ,Herpesvirus 4, Human ,Colony Count, Microbial ,Dental Plaque ,Cytomegalovirus ,Eikenella corrodens ,Papillon–Lefèvre syndrome ,Aggregatibacter actinomycetemcomitans ,Polymerase Chain Reaction ,Severe periodontitis ,Microbiology ,Autosomal recessive trait ,Papillon-Lefevre Disease ,Prevotella nigrescens ,medicine ,Humans ,Child ,Periodontitis ,biology ,medicine.disease ,biology.organism_classification ,Superinfection ,DNA, Viral ,Periodontics ,Female ,Fusobacterium nucleatum - Abstract
Papillon-Lefevre syndrome patients exhibit hyperkeratosis palmoplantaris and severe periodontitis. The syndrome is an autosomal recessive trait, but the mechanism of periodontal destruction is not known. This report presents the clinical and microbiological features of an 11-year old girl with Papillon-Lefěvre syndrome. Clinical examination included conventional periodontal measurements and radiographic analysis. In samples from 3 deep periodontal lesions, the occurrence of major suspected periodontopathic bacteria was determined by selective and non-selective culture and polymerase chain reaction (PCR) identification, and the presence of cytomegalovirus and Epstein-Barr type 1 virus by a nested-PCR detection method. 10 of 22 available teeth demonstrated severe periodontal breakdown. Major cultivable bacteria included Actinobacillus actinomycetemcomitans (3.4% of total isolates), Prevotella nigrescens (16.4%), Fusobacterium nucleatum (14.3%) and Peptostreptococcus micros (10.6%). A. actinomycetemcomitans, P. nigrescens, Porphyromonas gingivalis and Eikenella corrodens were identified by PCR analysis. The patient's non-affected parents and older brother revealed several periodontal pathogens but not A. actinomycetemcomitans. The viral examination demonstrated cytomegalovirus and Epstein-Barr type 1 virus in the subgingival sample of the Papillon-Lefevre syndrome patient. The father and brother yielded subgingival cytomegalovirus but not Epstein-Barr type 1 virus. We hypothesize that human herpesviruses in concert with A. actinomycetemcomitans play important roles in the development of Papillon-Lefevre syndrome periodontitis.
- Published
- 1999
47. Papillon-Lefe ̀vre syndrome: Neutrophil function in 15 cases from 4 families in Egypt
- Author
-
Khaled A. Ghaffara, Ronald S. Brownd, Fat’heya M. Zahranb, and Hosam M. Fahmyc
- Subjects
Adult ,Male ,Proband ,Blood Bactericidal Activity ,Adolescent ,Neutrophils ,Papillon–Lefèvre syndrome ,Consanguinity ,Papillon-Lefevre Disease ,Phagocytosis ,Humans ,Medicine ,Child ,General Dentistry ,business.industry ,Case-control study ,Infant ,Opsonin Proteins ,medicine.disease ,Pedigree ,Antibody opsonization ,Otorhinolaryngology ,Lytic cycle ,Case-Control Studies ,Child, Preschool ,Immunology ,Etiology ,Female ,Surgery ,Analysis of variance ,Oral Surgery ,business - Abstract
The primary purpose of this study was to investigate the periodontal pathologic cause of Papillon-Lefèvre syndrome by comparing, with respect to neutrophil function, probands with Papillon-Lefèvre syndrome from 4 families in Egypt, unaffected siblings of the probands, and age-matched and gender-matched control subjects.Family histories and clinical dermal and oral manifestations of Papillon-Lefèvre syndrome were evaluated for 15 affected members of 4 families with the syndrome, 10 siblings of the probands, and 7 age-matched and gender-matched controls. Phagocytic and intracellular killing (lytic activity) of polymorphonuclear neutrophils was evaluated for all subjects according to a modification of the method of Wilkinson; opsonization was evaluated according to a modification of the methods of Cutler et al. Data were analyzed by means of analysis of variance.Family pedigrees were plotted, and consanguinity was noted in 3 of the 4 families with Papillon-Lefèvre syndrome. The means and SDs for phagocytic killing, lytic activity, and opsonization indices were as follows: probands, 4.76+/-1.99, 0.42+/-0.20, and 0.84+/-0.07; unaffected siblings, 10.4+/-1.3, 3.3+/-0.3, and 0.84+/-0.07; controls, 10.8+/-0.8, 3.5+/-0.6, and 0.85+/-0.05. The phagocytic killing and lytic activity indices demonstrated significance between the probands and both siblings and controls (P.0005), whereas the opsonization index did not demonstrate significance between groups.Significantly decreased neutrophil function in probands with Papillon-Lefèvre syndrome was demonstrated with respect to neutrophil phagocytotic and lytic activity but not with respect to opsonization. Therefore, specific neutrophil dysfunction appears to be etiologically involved in this disorder.
- Published
- 1999
48. Subgingival microbial profile of Papillon-Lefevre patients assessed by DNA-probes
- Author
-
T. Lundgren, Panos N. Papapanou, Gunnar Dahlén, and Stefan Renvert
- Subjects
Adult ,DNA, Bacterial ,Male ,Adolescent ,Gingiva ,Prevotella ,Papillon–Lefèvre syndrome ,Biology ,Bacterial composition ,Aggregatibacter actinomycetemcomitans ,Prevotella intermedia ,Microbiology ,Papillon-Lefevre Disease ,stomatognathic system ,Eikenella corrodens ,Prevalence ,medicine ,Bacteroides ,Humans ,Severe periodontal disease ,Treponema ,Child ,Periodontitis ,Bacteria ,Fusobacterium nucleatum ,Peptostreptococcus ,Hybridization probe ,Nucleic Acid Hybridization ,Streptococcus ,Campylobacter ,medicine.disease ,biology.organism_classification ,stomatognathic diseases ,Adult periodontitis ,Periodontics ,Female ,DNA Probes ,Porphyromonas gingivalis ,Selenomonas - Abstract
The prevalence of 18 selected bacterial species was assessed by means of “checkerboard” DNA-DNA hybridisation in a group of 12 Saudi-Arabian adolescents with Papillon-Lefevre syndrome. A total of 36 tooth sites were investigated. The patients exhibited severe periodontal disease with deep pockets. All 12 patients harboured the putative bacterial pathogens P. intermedia, F. nucleatum, P. micros and S. intermedius while T. denticola, B. forsythus, P. nigrescens, E. corrodens, S. noxia and C. rectus were recovered from 11 patients. P. gingivalis was recovered from 9 patients and 18 sites while corresponding figures for A. actinomycetemcomitans were 8 and 19, respectively A number of the investigated species (B. forsythus, T. denticola, P. intermedia, C. rectus) reached high levels (≥106 cells) in more than 1/2 of the patients. On the other hand, bacteria such as A. actinomycetemcomitans and P. gingiyalis were infrequently encountered at high levels in these subgingival samples. In conclusion, the analysis failed to demonstrate a PLS-specific profile of the subgingival infection, since the bacterial composition of the sampled sites closely resembled that characterising deep pockets in adult periodontitis patients.
- Published
- 1998
49. Palmar plantar keratosis and unusual periodontal findings. Observations from a family of 4 members
- Author
-
O. Fardal, Ingar Olsen, and E. Drangsholt
- Subjects
Adult ,Male ,medicine.medical_specialty ,PLANTAR KERATOSIS ,Dentistry ,Papillon–Lefèvre syndrome ,Disease ,Aggregatibacter actinomycetemcomitans ,Oral hygiene ,Papillon-Lefevre Disease ,Periodontal disease ,Terminology as Topic ,Humans ,Medicine ,Child ,Periodontitis ,Porphyromonas gingivalis ,Plantar hyperkeratosis ,biology ,business.industry ,Prevotella intermedia ,Genetic Variation ,Middle Aged ,medicine.disease ,biology.organism_classification ,Dermatology ,Pedigree ,body regions ,stomatognathic diseases ,Periodontics ,Female ,business - Abstract
The connection between palmar plantar hyperkeratosis and severe periodontal disease was first reported in 1924 by Papillon and Lefevre. The 2 major components of this syndrome (PLS) can also occur as distinct entities. The literature describes a number of cases which do not fit the classical disease descriptions. In this paper, we report on a family with an atypical PLS. The father had marked palmar plantar hyperkeratosis but a very late onset of destructive marginal periodontitis. The son also had palmar plantar hyperkeratosis, but despite the fact that he initially harboured Actinobacillus actinomycetemcomitans, Prevotella intermedia and Porphyromonas gingivalis, he did not develop periodontal disease over a seven-year observation period when improved oral hygiene and professional tooth cleaning were instituted.
- Published
- 1998
50. Localisation of a gene for Papillon-Lefèvre syndrome to chromosome 11q14-q21 by homozygosity mapping
- Author
-
Hans Christian Hennies, Thomas F. Wienker, Irene M. Leigh, Martin Walter Laass, Howard P. Stevens, Martin Jung, Sabine Preis, and André Reis
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Candidate gene ,Adolescent ,Genotype ,Turkey ,Locus (genetics) ,Papillon–Lefèvre syndrome ,Biology ,Polymerase Chain Reaction ,Papillon-Lefevre Disease ,Genetic linkage ,Germany ,Genetics ,medicine ,Humans ,Child ,Gene ,Genetics (clinical) ,Chromosomes, Human, Pair 11 ,Homozygote ,Haplotype ,Chromosome Mapping ,Middle Aged ,Disease gene identification ,medicine.disease ,Pedigree ,Palmoplantar keratoderma ,Child, Preschool ,Female ,Ethiopia ,Lod Score ,Microsatellite Repeats - Abstract
Papillon-Lefèvre syndrome is an autosomal recessively inherited palmoplantar keratoderma of unknown aetiology associated with severe periodontitis leading to premature loss of dentition. Three consanguineous families, two of Turkish and one of German origin, and three multiplex families, one of Ethiopian and two of German origin, with 11 affected and 6 unaffected siblings in all were studied. A targeted genome search was initially attempted to several candidate gene regions but failed to demonstrate linkage. Therefore a genome-wide linkage scan using a combination of homozygosity mapping and traditional linkage analysis was undertaken. Linkage was obtained with marker D11S937 with a maximum two-point lod score of Zmax = 6.1 at recombination fraction theta = 0.00 on chromosome 11q14-q21 near the metalloproteinase gene cluster. Multipoint likelihood calculations gave a maximum lod score of 7.35 between D11S901 and D11S1358. A 9.2-cM region homozygous by descent in the affected members of the three consanguineous families lies between markers D11S1989 and D11S4176 harbouring the as yet unknown Papillon-Lefèvre syndrome gene. Haplotype analyses in all the families studied support this localisation. This study has identified a further locus harbouring a gene for palmoplantar keratoderma and one possibly involved in periodontitis.
- Published
- 1997
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.