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Mutation analysis of the cathepsin C gene in Indian families with Papillon-Lefèvre syndrome.

Selvaraju V, Markandaya M, Prasad PV, Sathyan P, Sethuraman G, Srivastava SC, Thakker N, Kumar A - BMC Med. Genet. (2003)

Bottom Line: This study reported three novel nonsense mutations in three Indian families.These novel nonsense mutations are predicted to produce truncated dipeptidyl-peptidase I causing PLS phenotype in these families.A review of the literature along with three novel mutations reported here showed that the total number of mutations in the CTSC gene described to date is 41 with 17 mutations being located in exon 7.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Reproduction Development and Genetics, Indian Institute of Science, Bangalore, India. selvacell@rediffmail.com

ABSTRACT

Background: PLS is a rare autosomal recessive disorder characterized by early onset periodontopathia and palmar plantar keratosis. PLS is caused by mutations in the cathepsin C (CTSC) gene. Dipeptidyl-peptidase I encoded by the CTSC gene removes dipeptides from the amino-terminus of protein substrates and mainly plays an immune and inflammatory role. Several mutations have been reported in this gene in patients from several ethnic groups. We report here mutation analysis of the CTSC gene in three Indian families with PLS.

Methods: Peripheral blood samples were obtained from individuals belonging to three Indian families with PLS for genomic DNA isolation. Exon-specific intronic primers were used to amplify DNA samples from individuals. PCR products were subsequently sequenced to detect mutations. PCR-SCCP and ASOH analyses were used to determine if mutations were present in normal control individuals.

Results: All patients from three families had a classic PLS phenotype, which included palmoplantar keratosis and early-onset severe periodontitis. Sequence analysis of the CTSC gene showed three novel nonsense mutations (viz., p.Q49X, p.Q69X and p.Y304X) in homozygous state in affected individuals from these Indian families.

Conclusions: This study reported three novel nonsense mutations in three Indian families. These novel nonsense mutations are predicted to produce truncated dipeptidyl-peptidase I causing PLS phenotype in these families. A review of the literature along with three novel mutations reported here showed that the total number of mutations in the CTSC gene described to date is 41 with 17 mutations being located in exon 7.

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Clinical features of PLS. (A) Periodontitis affecting secondary dentition in the patient IV-3 at 16 yrs of age from the family IISC-PLS2. (B) Orthopantomogram of oral cavity of patient IV-3 at 11 years of age from the family IISC-PLS2 with severe periodontitis. All teeth in this patient are permanent and there is an extensive loss of alveolar bone both in maxillary and mandibular arches. (C) Periodontitis in the patient IV-4 at 12 years of age from the family IISC-PLS2. (D) Orthopantomogram of oral cavity of patient IV-4 at 12 years of age from the family IISC-PLS2 with severe periodontitis. All teeth in this patient are permanent and there is an extensive loss of alveolar bone both in maxillary and mandibular arch. (E) Knuckle hyperkeratosis in the patient IV-4 of the family IISC-PLS2. (F) Plantar hyperkeratosis in the patient IV-3 of the family IISC-PLS2. (G) Palmar hyperkeratosis (punctate type) in the patient II-2 of the family IISC-PLS3.
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Figure 1: Clinical features of PLS. (A) Periodontitis affecting secondary dentition in the patient IV-3 at 16 yrs of age from the family IISC-PLS2. (B) Orthopantomogram of oral cavity of patient IV-3 at 11 years of age from the family IISC-PLS2 with severe periodontitis. All teeth in this patient are permanent and there is an extensive loss of alveolar bone both in maxillary and mandibular arches. (C) Periodontitis in the patient IV-4 at 12 years of age from the family IISC-PLS2. (D) Orthopantomogram of oral cavity of patient IV-4 at 12 years of age from the family IISC-PLS2 with severe periodontitis. All teeth in this patient are permanent and there is an extensive loss of alveolar bone both in maxillary and mandibular arch. (E) Knuckle hyperkeratosis in the patient IV-4 of the family IISC-PLS2. (F) Plantar hyperkeratosis in the patient IV-3 of the family IISC-PLS2. (G) Palmar hyperkeratosis (punctate type) in the patient II-2 of the family IISC-PLS3.

Mentions: All patients had a history of the onset of the disorder by the age of 2 to 3 years. Examination of these patients revealed that they all had severe palmar plantar keratoderma, and severe periodontitis (except individual II-2 from family IISC-PLS3) leading to shedding of most of their teeth. Patient II-2 from family IISC-PLS3 had a subsidence of periodontitis, as he was edentulous, having lost all his teeth by the age of 12 years. Patients IV-3 and IV-4 from family IISC-PLS2 also had hyperkeratosis of the knuckles, knees and elbows in addition to palmar plantar keratoderma and severe periodontitis. Fig. 1 illustrates clinical manifestations of PLS. Individual II-2 from family IISC-PLS3 was known to have frequent episodes of infections especially of the skin and recurrent fevers in childhood, suggesting an increased susceptibility to microbial infections. Heterozygous parents from families IISC-PLS1 and IISC-PLS2 and heterozygous siblings (IV-1 and IV-5) from family IISC-PLS2 were unaffected.


Mutation analysis of the cathepsin C gene in Indian families with Papillon-Lefèvre syndrome.

Selvaraju V, Markandaya M, Prasad PV, Sathyan P, Sethuraman G, Srivastava SC, Thakker N, Kumar A - BMC Med. Genet. (2003)

Clinical features of PLS. (A) Periodontitis affecting secondary dentition in the patient IV-3 at 16 yrs of age from the family IISC-PLS2. (B) Orthopantomogram of oral cavity of patient IV-3 at 11 years of age from the family IISC-PLS2 with severe periodontitis. All teeth in this patient are permanent and there is an extensive loss of alveolar bone both in maxillary and mandibular arches. (C) Periodontitis in the patient IV-4 at 12 years of age from the family IISC-PLS2. (D) Orthopantomogram of oral cavity of patient IV-4 at 12 years of age from the family IISC-PLS2 with severe periodontitis. All teeth in this patient are permanent and there is an extensive loss of alveolar bone both in maxillary and mandibular arch. (E) Knuckle hyperkeratosis in the patient IV-4 of the family IISC-PLS2. (F) Plantar hyperkeratosis in the patient IV-3 of the family IISC-PLS2. (G) Palmar hyperkeratosis (punctate type) in the patient II-2 of the family IISC-PLS3.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC183830&req=5

Figure 1: Clinical features of PLS. (A) Periodontitis affecting secondary dentition in the patient IV-3 at 16 yrs of age from the family IISC-PLS2. (B) Orthopantomogram of oral cavity of patient IV-3 at 11 years of age from the family IISC-PLS2 with severe periodontitis. All teeth in this patient are permanent and there is an extensive loss of alveolar bone both in maxillary and mandibular arches. (C) Periodontitis in the patient IV-4 at 12 years of age from the family IISC-PLS2. (D) Orthopantomogram of oral cavity of patient IV-4 at 12 years of age from the family IISC-PLS2 with severe periodontitis. All teeth in this patient are permanent and there is an extensive loss of alveolar bone both in maxillary and mandibular arch. (E) Knuckle hyperkeratosis in the patient IV-4 of the family IISC-PLS2. (F) Plantar hyperkeratosis in the patient IV-3 of the family IISC-PLS2. (G) Palmar hyperkeratosis (punctate type) in the patient II-2 of the family IISC-PLS3.
Mentions: All patients had a history of the onset of the disorder by the age of 2 to 3 years. Examination of these patients revealed that they all had severe palmar plantar keratoderma, and severe periodontitis (except individual II-2 from family IISC-PLS3) leading to shedding of most of their teeth. Patient II-2 from family IISC-PLS3 had a subsidence of periodontitis, as he was edentulous, having lost all his teeth by the age of 12 years. Patients IV-3 and IV-4 from family IISC-PLS2 also had hyperkeratosis of the knuckles, knees and elbows in addition to palmar plantar keratoderma and severe periodontitis. Fig. 1 illustrates clinical manifestations of PLS. Individual II-2 from family IISC-PLS3 was known to have frequent episodes of infections especially of the skin and recurrent fevers in childhood, suggesting an increased susceptibility to microbial infections. Heterozygous parents from families IISC-PLS1 and IISC-PLS2 and heterozygous siblings (IV-1 and IV-5) from family IISC-PLS2 were unaffected.

Bottom Line: This study reported three novel nonsense mutations in three Indian families.These novel nonsense mutations are predicted to produce truncated dipeptidyl-peptidase I causing PLS phenotype in these families.A review of the literature along with three novel mutations reported here showed that the total number of mutations in the CTSC gene described to date is 41 with 17 mutations being located in exon 7.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular Reproduction Development and Genetics, Indian Institute of Science, Bangalore, India. selvacell@rediffmail.com

ABSTRACT

Background: PLS is a rare autosomal recessive disorder characterized by early onset periodontopathia and palmar plantar keratosis. PLS is caused by mutations in the cathepsin C (CTSC) gene. Dipeptidyl-peptidase I encoded by the CTSC gene removes dipeptides from the amino-terminus of protein substrates and mainly plays an immune and inflammatory role. Several mutations have been reported in this gene in patients from several ethnic groups. We report here mutation analysis of the CTSC gene in three Indian families with PLS.

Methods: Peripheral blood samples were obtained from individuals belonging to three Indian families with PLS for genomic DNA isolation. Exon-specific intronic primers were used to amplify DNA samples from individuals. PCR products were subsequently sequenced to detect mutations. PCR-SCCP and ASOH analyses were used to determine if mutations were present in normal control individuals.

Results: All patients from three families had a classic PLS phenotype, which included palmoplantar keratosis and early-onset severe periodontitis. Sequence analysis of the CTSC gene showed three novel nonsense mutations (viz., p.Q49X, p.Q69X and p.Y304X) in homozygous state in affected individuals from these Indian families.

Conclusions: This study reported three novel nonsense mutations in three Indian families. These novel nonsense mutations are predicted to produce truncated dipeptidyl-peptidase I causing PLS phenotype in these families. A review of the literature along with three novel mutations reported here showed that the total number of mutations in the CTSC gene described to date is 41 with 17 mutations being located in exon 7.

Show MeSH
Related in: MedlinePlus