Abstract
BackgroundKeratoconus normally presents as a sporadic disease. Although different studies have found sequence variants of the visual system homeobox 1 (VSX1) gene associated with keratoconus in humans, no research has detected such variants in sporadic keratoconus patients from China. To investigate the possibility of VSX1 being a candidate susceptibility gene for Chinese patients with sporadic keratoconus, we performed sequence screening of this gene in such patients.MethodsWhole DNA was obtained from the leukocytes in the peripheral venous blood of 50 patients with sporadic keratoconus and 50 control subjects without this ocular disorder. Polymerase chain reaction single-strand conformation polymorphism analysis and direct DNA sequencing technology were used to detect sequence variation in the five exons and splicing regions of the introns of the VSX1 gene. The sequencing results were analyzed using DNAstar software.ResultsOne novel missense heterozygous sequence variant (p.Arg131Pro) was found in the first exon of the VSX1 gene in one keratoconus patient. Another heterozygous sequence variant (p.Gly160Val) in the second exon was found in two keratoconus patients. These variants were not detected in the control subjects. In the third intron of the VSX1 gene, c.8326G > A nucleotide substitution (including heterozygous and homozygous change) was also discovered. The frequency of this variation did not differ significantly between patients and controls, it should belong to single-nucleotide polymorphism of the VSX1 gene. Bioinformatic analysis also predicted that one missense sequence variation (p.Arg131Pro) may not cause a pathogenic change.ConclusionsIn this study, we added one novel missense sequence variation (p.Arg131Pro) in the coding region of the VSX1 gene to the range of VSX1 coding region variations observed in patients with sporadic keratoconus from China. Our work suggests that VSX1 sequence variants might be involved in the pathogenesis of sporadic keratoconus, but their precise role in disease causation requires further investigation.
Highlights
Keratoconus normally presents as a sporadic disease
PCR-SSCP results All exons of the visual system homeobox 1 (VSX1) gene in sporadic keratoconus patients were amplified by PCR
DNA sequencing results The 50 sporadic keratoconus patients and 50 control subjects recruited for this study underwent screening of the entire coding region and exon–intron junctions of the VSX1 gene by direct sequencing of DNA
Summary
Keratoconus normally presents as a sporadic disease. Different studies have found sequence variants of the visual system homeobox 1 (VSX1) gene associated with keratoconus in humans, no research has detected such variants in sporadic keratoconus patients from China. To investigate the possibility of VSX1 being a candidate susceptibility gene for Chinese patients with sporadic keratoconus, we performed sequence screening of this gene in such patients. Keratoconus is a congenital disease involving noninflammatory corneal ectasia. Most keratoconus cases are sporadic, about 6–10% of cases have been reported to have a positive family history. Keratoconus can exhibit dominant or recessive inheritance; with autosomal dominant inheritance, the disease exhibits variable phenotypes with incomplete penetrance [3, 4]. Slit lamp microscope examinations of keratoconus patients have demonstrated Vogt’s line, Fleischer’s ring, and corneal scarring [5,6,7]. Several treatment modalities are available, severe keratoconus remains an indication for corneal transplantation [8,9,10]
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