Postoperative chronic pain in arthroplasty papillon-lefèvre syndrome: 17-year dental follow-up: case report / Síndrome de papillon-lefèvre: seguimiento dental de 17 años: reporte de caso

Introduction: The present report describes the case of a 12-year-old patient with 17-year follow-up who was previously diagnosed with Papillon-Lefèvre Syndrome (PLS), which is a rare autosomal recessive irregularity in the cathepsin C gene (CTSC) characterized by palmoplantar hyperkeratosis and premature loss of primary and permanent teeth. Case Report: A specific mutation in the c.203 T > G gene inducing loss of function leading to PLS was detected, as was a mutation in the HLA-DRB1*11 allele, which is associated with this syndrome. There is no consanguinity of the parents, and the siblings are entirely healthy. Early identification of the main characteristics of this syndrome is imperative. Accurate diagnosis by genetic analysis allows differential diagnoses and timely comprehensive dental treatment. Conclusions: Additionally, it allows consultation with a dermatologist to maintain or improve the quality of life of patients with this condition due to progressive worsening and severity of the main physical manifestations. Keywords: Papillon-Lefevre Disease; Keratoderma, Palmo-plantar; Cathepsin C; Periodontitis; Skin Diseases, Genetic; Case reports

Introducción: El presente reporte describe el caso de un paciente de 12 años de edad con 17 años de seguimiento a quien previamente se le diagnosticó Síndrome de Papillon-Lefèvre (PLS), el cual es una rara irregularidad autosómica recesiva en el gen de la catepsina C (CTSC) caracterizada por hiperqueratosis palmoplantar y pérdida prematura de dientes primarios y permanentes. Reporte de Caso: Se detectó una mutación específica en el gen c.203 T > G que induce pérdida de función que conduce a PLS, así como una mutación en el alelo HLA-DRB1*11, que se asocia a este síndrome. No presenta consanguinidad de los padres, padres y hermanos totalmente sanos. La identificación temprana de las principales características de este síndrome es imperativa. El diagnóstico certero por análisis genético permite diagnósticos diferenciales y tratamientos odontológicos integrales oportunos. Conclusiones: Adicionalmente, permite la consulta con un dermatólogo para mantener o mejorar la calidad de vida de los pacientes con esta condición debido al progresivo empeoramiento y severidad de las principales manifestaciones físicas.

Gene mutational analyses of cathepsin C gene in a family with Papillon-Lefèvre syndrome / 华西口腔医学杂志

OBJECTIVE@#This study aimed to investigate the gene mutational characteristics of cathepsin C (CTSC) gene in a Chinese patient with Papillon-Lefèvre syndrome (PLS) and further confirm the genetic basis for the phenotype of PLS.@*METHODS@#Peripheral blood samples were obtained from the PLS proband and his family members (his parents and younger brother) for genomic DNA extraction. The coding region and exon boundaries of the CTSC gene were amplified and sequenced by polymerase chain reaction and direct sequencing of DNA.@*RESULTS@#Compound heterozygous mutations of CTSC gene were identified in the patient. A heterozygous missense mutation occurred in the 800th base of exon 6, and the base T in the base pair was replaced by C (c.800T>C). The encoded amino acid leucine changed to proline (p. L267P). A heterozygous missense mutation occurred in the 1015th base of exon 7, and base C in the base pair was replaced by T (c.1015C>T). The encoded amino acid arginine changed to cysteine (p.R339C). Among the mutations, c.800T>C originated from the mother, c.1015C>T was identified from the father. No mutations were detected in the younger brother.@*CONCLUSIONS@#Mutations of CTSC gene are responsible for the phenotype of PLS.

Molecular characterization and expression analysis of cathepsin C in Chinese giant salamander (Andrias davidianus) after Aeromonas hydrophila infection

Background: Cathepsin C (CTSC) (dipeptidyl peptidase I, DPPI), is a member of the papain superfamily of cysteine proteases and involves in a variety of host reactions. However, the information of CTST in Chinese giant salamander (Andrias davidianus), an amphibian species with important evolutionary position and economic values, remained unclear. Results: The full-length salamander CTSC cDNA contained a 96 bp of 5'-UTR, a 1392 bp of ORF encoding 463 amino acids, and a 95 bp of 3'-UTR. The salamander CTSC possessed several sequence features similar to other reported CTSCs such as a signal peptide, a propeptide and a mature peptide. The active site triad of Cys, His and Asn were also found existing in salamander CTSC. Salamander CTSC mRNA was constitutively expressed in all the examined tissues with significantly variant expression level. The highest expression of CTSC was in intestine, followed with stomach, spleen, lung and brain. Following Aeromonas hydrophila infection for 12 h, salamander CTSC was significantly up-regulated in several tissues including lung, spleen, brain, kidney, heart, stomach and skin. Conclusion: CTSC plays roles in the immune response to bacterial infection, which provided valuable information for further studying the functions of CTSC in salamander.

DNA Vaccines Encoding Toxoplasma gondii Cathepsin C 1 Induce Protection against Toxoplasmosis in Mice

Toxoplasma gondii cathepsin C proteases (TgCPC1, 2, and 3) are important for the growth and survival of T. gondii. In the present study, B-cell and T-cell epitopes of TgCPC1 were predicted using DNAstar and the Immune Epitope Database. A TgCPC1 DNA vaccine was constructed, and its ability to induce protective immune responses against toxoplasmosis in BALB/c mice was evaluated in the presence or absence of the adjuvant α-GalCer. As results, TgCPC1 DNA vaccine with or without adjuvant α-GalCer showed higher levels of IgG and IgG2a in the serum, as well as IL-2 and IFN-γ in the spleen compared to controls (PBS, pEGFP-C1, and α-Galcer). Upon challenge infection with tachyzoites of T. gondii (RH), pCPC1/α-Galcer immunized mice showed the longest survival among all the groups. Mice vaccinated with DNA vaccine without adjuvant (pCPC1) showed better protective immunity compared to other controls (PBS, pEGFP-C1, and α-Galcer). These results indicate that a DNA vaccine encoding TgCPC1 is a potential vaccine candidate against toxoplasmosis.

Gene mutational analyses of the cathepsin C gene in families with Papillon-Lefèvre syndrome / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aims to investigate the gene mutational characteristics of cathepsin C (CTSC) gene in a Chinese patient with Papillon-Lefèvre syndrome (PLS), then further confirm the genetic basis for the phenotype of PLS, and obtain genetic information that can be used as guide in the diagnosis and treatment of PLS.</p><p><b>METHODS</b>With their consent, peripheral blood samples were obtained from the proband and his family members (his parents and older sister) for genomic DNA extraction. The coding region and exon/intron boundaries of the CTSC gene were amplified and sequenced using poly-merase chain reaction and direct sequencing of DNA.</p><p><b>RESULTS</b>Compound heterozygous mutations of CTSC gene were iden-tified in the patient. The proband carries one heterozygous nonsense mutation c.754C>T in exon 5 and one heterozygous missense mutation c.1040A>G in exon 7. Both parents were heterozygous carriers without the clinical symptoms of PLS. None of the mutations were detected in the proband's sister.</p><p><b>CONCLUSIONS</b>The study proves that mutations of CTSC gene are responsible for the phenotype of Papillon-Lefèvre syndrome.
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Screening of CTSC gene mutations in a Chinese pedigree affected with Papillon-Lefevre syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the clinical phenotype of a Chinese pedigree affected with Papillon-Lefevre syndrome(PLS) and detect mutation of CTSC gene.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>A homozygous mutation c.901G>A (p.G301S) in exon 7 of CTSC gene was identified in the patient. Both parents of the patient had carried a heterozygous c.901G>A 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.</p><p><b>CONCLUSION</b>The c.901G>A mutation of the CTSC gene was first reported in China, which has expanded its mutation spectrum.</p>

Papillon-Lefevre syndrome: a case report of two siblings and review of the literature

Papillon-Lefevre syndrome is a rare autosomal recessive genodermatosis which is characterised by periodontitis, palmoplantar keratoderma and predisposition to pyogenic infections and occurs due to cathepsin C gene mutation [located on chromosome11].The loss of primary teeth usually occurs by the age of 4 years and secondary teeth by second decade. The disorder is associated with significant cosmetic and functional disability

Two Cases of Papillon-Lefevre Syndrome / 대한피부과학회지

Papillon-Lefevre syndrome is an extremely rare genodermatosis characterized by palmoplantar keratoderma and premature loss of teeth. It is inherited as an autosomal recessive trait, and is known to be caused by a loss-of-function mutation in the cathepsin C gene. Mutations of this gene may result in epithelial defects producing keratoderma and secondary periodontitis recalcitrant to traditional treatment, causing subsequent premature loss of teeth. In addition, patients may have increased susceptibility to infection. Histopathologic features are nonspecific, so diagnosis has been made through characteristic skin and teeth findings in many reported cases. Oral retinoids are the mainstay of treatment, but the safety of oral retinoids in children remains controversial due to their side effects in skeletal development. Therefore, a multidisciplinary approach is important for the care of patients with this syndrome. We present two cases of Papillon-Lefevre syndrome. To our knowledge, this condition has not been reported previously in the Korean dermatologic literature.

Altered Gene Expression in Cerulein-Stimulated Pancreatic Acinar Cells: Pathologic Mechanism of Acute Pancreatitis

Acute pancreatitis is a multifactorial disease associated with the premature activation of digestive enzymes. The genes expressed in pancreatic acinar cells determine the severity of the disease. The present study determined the differentially expressed genes in pancreatic acinar cells treated with cerulein as an in vitro model of acute pancreatitis. Pancreatic acinar AR42J cells were stimulated with 10(-8) M cerulein for 4 h, and genes with altered expression were identified using a cDNA microarray for 4,000 rat genes and validated by real-time PCR. These genes showed a 2.5-fold or higher increase with cerulein: lithostatin, guanylate cyclase, myosin light chain kinase 2, cathepsin C, progestin-induced protein, and pancreatic trypsin 2. Stathin 1 and ribosomal protein S13 showed a 2.5-fold or higher decreases in expression. Real-time PCR analysis showed time-dependent alterations of these genes. Using commercially available antibodies specific for guanylate cyclase, myosin light chain kinase 2, and cathepsin C, a time-dependent increase in these proteins were observed by Western blotting. Thus, disturbances in proliferation, differentiation, cytoskeleton arrangement, enzyme activity, and secretion may be underlying mechanisms of acute pancreatitis.

Mutational analysis of the cathepsin C gene in a family of Han nationality with Papillon-Lefevre syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the mutational characteristics of the cathepsin C gene (CTSC, also known as dipeptidyl-peptidase I gene, DPP I) in a family of Han nationality with Papillon-Lefevre syndrome, and to provide the molecular basis for the phenotype.</p><p><b>METHODS</b>Genomic DNAs were extracted from the proband, his parents and younger sister after informed consent. Polymerase chain reaction and direct DNA sequencing were carried out to screen the mutations of the cathepsin C gene.</p><p><b>RESULTS</b>Compound heterozygous mutations of the cathepsin C gene were identified in the patient. The patient carried one frameshift mutation 116delG in exon 1, one heterozygous mutation C255S in exon 6, one missense mutation F314S and one sense mutation E335E in exon 7. The four changes were novel mutations of the cathepsin C gene, which had not been reported previously. None of the mutations were detected in normal controls.</p><p><b>CONCLUSION</b>Mutations of the cathepsin C gene are probably responsible for the phenotype of Papillon-Lefevre syndrome in this family.</p>

Papillon Lefevre syndrome.

Papillon Lefèvre syndrome is a rare disease characterized by skin lesions caused by palmar-plantar hyperkeratosis, and severe periodontal destruction involving both the primary and permanent dentitions. It is transmitted as an autosomal recessive condition and consanguinity of parents is evident in about one-third of cases. Pyogenic liver abscess is an increasingly recognized complication. We report a new case of this association and review the current literature.

Novel mutations of cathepsin C gene in two Chinese patients with Papillon-Lefèvre syndrome / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the mutational characteristics of cathepsin C (CTSC) gene in two Chinese patients with Papillon-Lefèvre syndrome (PLS), and provide molecular basis for research of the pathogenesis of PLS.</p><p><b>METHODS</b>Peripheral blood samples were obtained from patients and their parents respectively. Genomic DNA were extracted after consents. Polymerase chain reaction, direct DNA sequencing and restriction enzyme reaction were performed to screen mutations of CTSC gene.</p><p><b>RESULTS</b>Compound heterozygous mutations of CTSC gene were identified in the two patients. Patient I carried the G139R and S260P mutations, patient II had the R250X and C258W mutations. The parents were heterozygous carriers without the clinical feature of PLS. None of the mutations were detected in normal controls. Furthermore, the S260P and C258W changes were novel mutations of CTSC gene, which had not been reported previously.</p><p><b>CONCLUSIONS</b>Mutations of CTSC gene are responsible for the phenotype of Papillon-Lefèvre syndrome in two Chinese patients. The results extend the mutation spectrum of CTSC gene and also provide basis for gene diagnosis of PLS in China.</p>

Identification of Gene Expression Signatures in Korean Acute Leukemia Patients

BACKGROUND: In acute leukemia patients, several successful methods of expression profiling have been used for various purposes, i.e., to identify new disease class, to select a therapeutic target, or to predict chemo-sensitivity and clinical outcome. In the present study, we tested the peripheral blood of 47 acute leukemia patients in an attempt to identify differentially expressed genes in AML and ALL using a Korean-made 10K oligo-nucleotide microarray. METHODS: Total RNA was prepared from peripheral blood and amplified for microarray experimentation. SAM (significant analysis of microarray) and PAM (prediction analysis of microarray) were used to select significant genes. The selected genes were tested for in a test group, independently of the training group. RESULTS: We identified 345 differentially expressed genes that differentiated AML and ALL patients (FWER < 0.05). Genes were selected using the training group (n=35) and tested for in the test group (n=12). Both training group and test group discriminated AML and ALL patients accurately. Genes that showed relatively high expression in AML patients were deoxynucleotidyl transferase, pre-B lymphocyte gene 3, B-cell linker, CD9 antigen, lymphoid enhancer-binding factor 1, CD79B antigen, and early B-cell factor. Genes highly expressed in ALL patients were annexin A 1, amyloid beta (A4) precursor protein, amyloid beta (A4) precursor-like protein 2, cathepsin C, lysozyme (renal amyloidosis), myeloperoxidase, and hematopoietic prostaglandin D2 synthase. CONCLUSION: This study provided genome wide molecular signatures of Korean acute leukemia patients, which clearly identify AML and ALL. Given with other reported signatures, these molecular signatures provide a means of achieving a molecular diagnosis in Korean acute leukemia patents.