ABSTRACT

Purpose

Keratoconus (KC) is a corneal ectasia disease with complex genetic heterogeneity. The present study aimed to identify susceptibility genes in Chinese patients with KC.

Methods

Exome sequencing (ES) was performed in 28 Chinese KC patients to search for susceptibility genes of the disease. The candidate variants were filtered out by multi-step bioinformatics analysis and validated by Sanger sequencing. Another 100 individuals with KC were also recruited to verify those variants by Sanger sequencing.

Results

By filtering out nonsynonymous variants located in exon, selecting variants which were presented in two or more samples and applying public databases to remove common variants, along with the inclusion of missense SNVs located in differential expressed genes and protein damaging variants (stop gain/stop loss SNVs and InDels), we have identified 6 SNVs (4 missense SNVs: c.1168 T > C in TRANK1, c.341A>T in ERMP1, c.4346 T > C in SDK2, c.1730A>C in COL6A1; 2 stop gain SNVs: c.1138 C > T in CNBD1, c.241 C > T in KRT82) and 2 InDels (c.193_195del in NSUN5, c.1690_1698del in COL9A3) as candidate variants for KC. The verifying results showed that c.341A>T in ERMP1 and c.193_195del in NSUN5 was found in one and two samples, respectively.

Conclusions

Our study suggested that a total of six SNVs in six genes and two InDels in two genes might be considered as candidate variants in Chinese patients with KC.