Mutation analysis of VSX1 gene in vernal keratoconjunctivitis patients

Abstract

Objectives: Vernal keratoconjunctivitis (VKC) is a multifactorial disease of conjunctiva that usually involves young adults. Heretofore, the role of several genes has been studied in VKC pathogenesis. The aim of this study was to discover new modifications in Visual System Homeobox 1 (VSX1) gene and evaluate their possible correlation with the protein activity and VKC pathogenesis in Iranian patients. Methods: For this cross-sectional study, DNA samples of 100 sporadic patients with VKC and 100 healthy people were analyzed for detection of novel mutations in exon 3, intron 3 and exon 4 of VSX1 gene, using single strand conformation polymorphism (SSCP) and heteroduplex analysis (HA). After DNA sequencing of samples with different SSCP and HA pattern, conservation level and pathogenicity of the detected variations were investigated using bioinformatics software and databases. Results: Sequencing results revealed a (c. 628-31 T > A) g. 25,075,355 T > A variation in intron 3 and a c.697G > A variation in the coding region of exon 4. RFLP results did not confirm the existence of c.697G > A mutation in the control group and this missense variation was recognized as a pathogenic risk factor, using SIFT software (P SIC > 2). Conclusion: Since the modified sequence is located within the conserved region, it can be proposed that the detected modification may have an effect on the encoded protein function. Nevertheless, more studies are required for analyzing and evaluating the exact effects of this substitution.