Exome sequencing identification of susceptibility genes in Chinese patients with keratoconus

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 inTRANK1, c.341A>T inERMP1, c.4346 T > C inSDK2, c.1730A>C inCOL6A1; 2 stop gain SNVs: c.1138 C > T inCNBD1, c.241 C > T inKRT82) and 2 InDels (c.193_195del inNSUN5, c.1690_1698del inCOL9A3) as candidate variants for KC. The verifying results showed that c.341A>T inERMP1and c.193_195del inNSUN5was 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.