Sequence analysis of the VSX1 and SOD1 genes in families with Keratoconus and a review of the literature

ObjectiveKeratoconus (KC) is a non-inflammatory disorder of the cornea in which the cornea becomes thin and conical, inducing myopia and irregular astigmatism and resulting in mild to marked impairment of vision. The present study was designed to screen two candidate KC genes to identify pathogenic sequence variants responsible for KC in Saudi families.MethodsPeripheral blood samples from members of five Saudi families with KC from the Northern region were collected. Genomic DNA was isolated, and bidirectional sequencing was performed of all coding exons of VSX1 and SOD1 genes using Sanger sequencing.ResultsAll five of the KC families showed a pattern of autosomal recessive inheritance. Phenotyping of these families was performed by a senior ophthalmologist. Sequence analysis of the VSX1 and SOD1 genes failed to reveal any pathogenic sequence variant that could account for KC in the affected individuals.ConclusionOur failure to detect sequence variants in two of the known KC associated genes triggers an interest in other known KC candidate genes, including miR-184, DOCK9, IL1RN and SLC4A11. Future genotyping with dense SNP arrays followed by exome sequencing in these families will be a useful approach to identify the gene(s) underlying KC in this Saudi cohort, which may be different from those reported elsewhere.