Heterozygous Ile453Val codon mutation in exon 7, homozygous single nucleotide polymorphisms in intron 2 and 5 of cathepsin C are associated with Haim-Munk syndrome

ABSTRACT

Objective: In the present study, we have investigated the genetic status of CTSC gene in a HMS subject, who along with her parents belonged to non-Jewish South Indian Dravidian community. Materials and Methods: Genomic deoxyribonucleic acid isolated from the peripheral blood of the subject was amplified with CTSC exon specific primers and were analyzed by direct sequencing. Results: Sequencing analysis identified Ile453Val mutation within exon 7 of CTSC gene in heterozygous condition, and two single nucleotide polymorphisms (SNPs) within intron 2 and 5 in homozygous condition. Conclusion: The present study has identified for the first time the association of Ile453Val mutation within exon 7 and the two SNPs in a subject with HMS.

Key words:

Cathepsin C mutation - Hain-Munk syndrome - Hain-Munk syndrome in India - single nucleotide polymorphism in Hain-Munk syndrome

• REFERENCES

• 1 Hart TC, Hart PS, Michalec MD, Zhang Y, Firatli E, Van Dyke TE. et al. Haim-Munk syndrome and Papillon-Lefèvre syndrome are allelic mutations in cathepsin C. J Med Genet 2000; 37: 88-94
• 2 Pahwa P, Lamba AK, Faraz F, Tandon S. Haim-Munk syndrome. J Indian Soc Periodontol 2010; 14: 201-3
• 3 Hacham-Zadeh S, Schaap T, Cohen MM. A genetic analysis of the Papillon-Lefèvre syndrome in a Jewish family from Cochin. Am J Med Genet 1978; 2: 153-7
• 4 Stevens HP, Kelsell DP, Bryant SP, Bishop DT, Spurr NK, Weissenbach J. et al. Linkage of an American pedigree with palmoplantar keratoderma and malignancy (palmoplantar ectodermal dysplasia type III) to 17q24. Literature survey and proposed updated classification of the keratodermas. Arch Dermatol 1996; 132: 640-51
• 5 Erciyas K, Inaloz S, Erciyas AF. Periodontal manifestations in a patient with Haim-Munk syndrome. Eur J Dent 2010; 4: 338-40
• 6 Romero-Quintana JG, Frías-Castro LO, Arámbula-Meraz E, Aguilar-Medina M, Dueñas-Arias JE, Melchor-Soto JD. et al. Identification of novel mutation in cathepsin C gene causing Papillon-Lefèvre Syndrome in Mexican patients. BMC Med Genet 2013; 14: 7
• 7 Janjua SA, Iftikhar N, Hussain I, Khachemoune A. Dermatologic, periodontal, and skeletal manifestations of Haim-Munk syndrome in two siblings. J Am Acad Dermatol 2008; 58: 339-44
• 8 Rai R, Thiagarajan S, Mohandas S, Natarajan K, Shanmuga Sekar C, Ramalingam S. Haim Munk syndrome and Papillon Lefevre syndrome – Allelic mutations in cathepsin C with variation in phenotype. Int J Dermatol 2010; 49: 541-3
• 9 Conus S, Simon HU. Cathepsins and their involvement in immune responses. Swiss Med Wkly 2010; 140: w13042
• 10 Nakagawa TY, Rudensky AY. The role of lysosomal proteinases in MHC class II-mediated antigen processing and presentation. Immunol Rev 1999; 172: 121-9
• 11 Reiser J, Adair B, Reinheckel T. Specialized roles for cysteine cathepsins in health and disease. J Clin Invest 2010; 120: 3421-31
• 12 Cury VF, Gomez RS, Costa JE, Friedman E, Boson W, De Marco L. A homozygous cathepsin C mutation associated with Haim-Munk syndrome. Br J Dermatol 2005; 152: 353-6
• 13 Noack B, Görgens H, Hempel U, Fanghänel J, Hoffmann T, Ziegler A. et al. Cathepsin C gene variants in aggressive periodontitis. J Dent Res 2008; 87: 958-63