Humans ; Papillon-Lefevre Disease

Papillon-Lefevre syndrome (PLS) is an extremely rare inherited disease as an autosomal recessive trait. The disorder is characterized by diffuse palmoplantar keratoderma and premature loss of both deciduous and permanent teeth. This paper described a case of PLS with classic clinical features and briefly reviewed the relevant literature.
Humans ; Papillon-Lefevre Disease

Papillon-Lefèvre syndrome (PLS) is a very rare syndrome of autosomal recessive inheritance characterized by palmoplantar hyperkeratosis and a severe destructive periodontitis, leading to premature loss of both primary and permanent dentitions. This article reported a boy who was diagnosed as having PLS.
Humans ; Papillon-Lefevre Disease ; Periodontitis

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.
Cathepsin C ; Child ; Humans ; Keratoderma, Palmoplantar ; Papillon-Lefevre Disease ; Periodontitis ; Retinoids ; Skin ; Tooth

Mal de Meleda (MDM), also known as keratoderma palmoplantaris transgrediens, is a rare inherited form of palmoplantar keratoderma. It is characterized by erythema and hyperkeratosis of the palms and soles, extending to the dorsal aspects of the hands and feet. A 15-year-old Korean female presented with sharply demarcated hyperkeratotic plaques on the palms and soles, which extended to the dorsal surfaces of the hands and feet, in a "glove-and-socks" distribution. The histopathologic study showed marked hyperkeratosis, acanthosis, and normogranulosis, without epidermolysis. Her genetic study detected compound heterozygous mutation in exon 3 of the ARS gene encoding SLURP-1. Family history did not reveal any other affected members and no consanguineous relationship was found. In view of these findings, we diagnosed this case as the first reported sporadic case of MDM in Korea, the farthest location from the endemic island of Meleda.
Adolescent ; Erythema ; Exons ; Female ; Foot ; Hand ; Humans ; Keratoderma, Palmoplantar ; Korea ; Papillon-Lefevre Disease

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.
Cathepsin C ; genetics ; DNA Mutational Analysis ; Exons ; Humans ; Male ; Mutation ; Papillon-Lefevre Disease ; genetics ; Pedigree ; Phenotype

Papillon-Lefevre syndrome (PLS) is an extremely rare autosomal recessive disorder characterized by palmoplantar keratoderma and periodontitis and occuring with an estimated incidence of 1-4 cases per million. Patients with PLS are highly susceptible to infection. The etiology of an infective susceptibility is unknown; however, an association with defects in neurophil dysfunction, insufficient lymphocyte response to pathogens, defects in monocyte functions and impairment of NK cell cytotoxic function has been suggested. To our knowledge, this is the first case report of atypical maxillary sinusitis accompanied by PLS, and we represent the case with a review of the related literatures.
Humans ; Incidence ; Keratoderma, Palmoplantar ; Killer Cells, Natural ; Lymphocytes ; Maxillary Sinus ; Maxillary Sinusitis ; Monocytes ; Papillon-Lefevre Disease ; Periodontitis

OBJECTIVEThis 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.

METHODSWith 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.

RESULTSCompound 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.

CONCLUSIONSThe study proves that mutations of CTSC gene are responsible for the phenotype of Papillon-Lefèvre syndrome.
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Asian Continental Ancestry Group ; Base Sequence ; Cathepsin C ; DNA ; DNA Mutational Analysis ; Exons ; Humans ; Mutation ; Papillon-Lefevre Disease ; Phenotype

OBJECTIVETo analyze the clinical phenotype of a Chinese pedigree affected with Papillon-Lefevre syndrome(PLS) and detect mutation of CTSC gene.

METHODSClinical 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.

RESULTSA 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.

CONCLUSIONThe c.901G>A mutation of the CTSC gene was first reported in China, which has expanded its mutation spectrum.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Cathepsin C ; genetics ; Child, Preschool ; China ; Exons ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Papillon-Lefevre Disease ; enzymology ; genetics ; Pedigree

OBJECTIVETo 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.

METHODSPeripheral 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.

RESULTSCompound 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.

CONCLUSIONSMutations 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.

Asian Continental Ancestry Group ; genetics ; Cathepsin C ; genetics ; Child, Preschool ; Exons ; genetics ; Female ; Humans ; Male ; Mutation, Missense ; genetics ; Papillon-Lefevre Disease ; enzymology ; genetics