Identification of seven novel mutations in keratoconus patients in a Han Chinese population.

PURPOSE

To test for the potential presence of novel mutations in the () gene in patients with sporadic keratoconus (KC) from a Han Chinese population.

METHODS

Fifty-three patients with primary KC, 30 patients with high myopia (HM), and 100 unrelated population-matched healthy controls without any ocular or systemic disorders, all of Han Chinese ethnicity, were recruited. Blood samples were donated, and genomic DNA was isolated from peripheral blood leukocytes. Sequence variations in were initially identified in patients with KC with next-generation sequencing and subsequently confirmed using Sanger sequencing. Sequence variants identified in patients with KC were subsequently screened in 30 patients with HM and 100 healthy control subjects. Other genes that were reported to be related to KC were also screened in the patients with KC who carried the mutations in . The Sorting Intolerant Form Tolerant (SIFT) program was used to predict the effect of amino acid substitution on the ZNF469 protein.

RESULTS

Sixteen sequence variants in the coding regions of were identified in this Chinese KC cohort. After five known single nucleotide polymorphisms (SNPs), one false-positive result, and three mutations that were also detected in the results of the whole-exome sequencing (WES) data performed in 220 Han Chinese individuals without ocular abnormalities were removed, seven novel mutations in (c.2059G>A, c.2137C>A, c.3466G>A, c.3749C>T, c.4300G>A, c.4684G>A, and c.7262G>A) that were predicted to be potentially damaging were identified. The patient with KC with the c.3466G>A mutation was also shown to carry one dedicator of cytokinesis 9 () mutation (c.1940C>T). None of the mutations were detected in the patients with HM or the healthy controls. All of the seven mutations in the patients with KC were heterozygote.

CONCLUSIONS

The results suggested for the first time that has a pathogenic role in Chinese patients with KC and have widened the mutation spectrum of KC in the Han Chinese population.