Research article

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

Veeriah Selvaraju¹ , Manjunath Markandaya¹ , Pullabatla Venkata Siva Prasad² , Parthasarathy Sathyan³ , Gomathy Sethuraman⁴ , Satish Chandra Srivastava¹ , Nalin Thakker⁵ and Arun Kumar¹

¹Department of Molecular Reproduction Development and Genetics, Indian Institute of Science, Bangalore, India

²Department of Dermatology, Rajah Muthiah Medical College Hospital, Annamalai University, Chidambaram, India

³Aravind Eye Hospital, Coimbatore, India

⁴Department of Dermatology, All India Institute of Medical Sciences, New Delhi, India

⁵Department of Medical Genetics and Dentistry, University of Manchester, UK

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BMC Medical Genetics 2003, 4:5doi:10.1186/1471-2350-4-5

Published:	12 July 2003

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.