Mutational screening of , , , , , and in a Chinese cohort of 103 patients with nonsyndromic high myopia.

PURPOSE

High myopia (HM) is one of the leading causes of irreversible vision loss in the world. Many myopia loci have been uncovered with linkage analysis, genome-wide association studies, and sequencing analysis. Numerous pathogenic genes within these loci have been detected in a portion of HM cases. In the present study, we aimed to investigate the genetic basis of 103 patients with nonsyndromic HM, focusing on the reported causal genes.

METHODS

A total of 103 affected individuals with nonsyndromic HM were recruited, including 101 patients with unrelated sporadic HM and a mother and son pair. All participants underwent comprehensive ophthalmic examinations, and genomic DNA samples were extracted from the peripheral blood. Whole exome sequencing was performed on the mother and son pair as well as on the unaffected father. Sanger sequencing was used to identify mutations in the remaining 101 patients. Bioinformatics analysis was subsequently applied to verify the mutations.

RESULTS

An extremely rare mutation in (c.2627A>T, p.K876M) was identified in the mother and son pair but not in the unaffected father. Another two mutations in (c.4787C>T, p.P1596L/c.5056G>A, p.G1686S) were identified in two unrelated patients. A total of eight heterozygous variants potentially affecting the protein function were detected in eight of the remaining 99 patients, including c.1350delC, p.V451Cfs76 and c.1023_1024insA, p.P342Tfs41 in ; c.244_246delAAG, p.K82del in ; c.545A>G, p.Y182C in ; c.415C>T, p.P139S in ; c.3266A>G, p.Y1089C in ; and c.2252C>T, p.S751L and c.1708C>T, p.R570C in . Multiple bioinformatics analyses were conducted, and a comparison to a group with geographically matched controls was performed, which supported the potential pathogenicity of these variants.

CONCLUSIONS

We provide further evidence for the potential role of in HM inheritance and enlarged the current genetic spectrum of nonsyndromic HM by comprehensively screening the reported causal genes.