Analysis of the VSX1 gene in sporadic keratoconus patients from China

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.

Genetic Aspects of Keratoconus: A Literature Review Exploring Potential Genetic Contributions and Possible Genetic Relationships with Comorbidities

“…It has also been observed that there are six transcripts and five variants which encode a truncated protein, while two of them retain the DNA-binding domain [ 261 ]. The five exons of VSX1 encode a protein consisting of 365 amino acids with a homeobox DNA-binding domain, a ceh-10 domain, and a Chx10/VSX1 domain [ 166 , 249 , 262 ]. The mRNA from the VSX1 gene is detected in embryonic craniofacial tissue, in the inner layer of the retina, and in the cornea [ 249 , 257 , 258 ].…”

Risk factors and severity of keratoconus on the East Coast of China

“…Based on such a huge population, the number of potential KC patients might be enormous in China. Articles have unveiled the relationship between KC associated genetic loci (VSX1, IL1A, IL1B, COL4A3 and COL4A4) and Chinese Han ethnicity [10][11][12] . However, epidemiological study of KC among Chinese population is kind of a blank, except a research from Singapore in which only 60.3% of their subjects were made up of Chinese in 2011 and a research that simply illustrated several clinical features of Chinese KC patients in 2005 13,14 .…”

A Novel Splice-Site Variation in COL5A1 Causes Keratoconus in an Indian Family

“…KC is characterized by the thinning of the central cornea and change in corneal shape, thereby leading to myopia and irregular astigmatism. Although the majority of KC cases are sporadic, genes correlated with KC, including VSX1 , have been reported [1, 2]. Furthermore, it has been reported that approximately 6–10% of KC patients have a familial history of the disease [3, 4].…”