Mutation screening of 17 candidate genes in a cohort of 67 probands with early-onset high myopia

Ophthalmic Physiol Opt. 2020 May;40(3):271-280. doi: 10.1111/opo.12683. Epub 2020 Mar 25.


Purpose: To detect variants in 17 known potentially causative genes for non-syndromic myopia in 67 Tujia Chinese patients with early-onset high myopia (eo-HM).

Methods: DNA from 67 unrelated patients with early onset (<7 years old) high myopia (refraction error ≤ -6.00D or axial length > 26 mm) were subjected to whole-exome sequencing (WES). Variants in 17 candidate genes were analysed by multistep bioinformatics analysis. Subsequently, Sanger sequencing was used to verify identified candidate mutations and to assess available family members for co-segregation with myopia.

Results: A multistep systematic analysis of variants in 17 potentially causative genes for eo-HM revealed four novel pathogenic mutations and three potential pathogenic mutations in 4 of 17 genes in 7 of 67 (10.4%) probands. The pathogenic group included one missense mutation (c.100G > C, p.Asp34His) and one splice donor mutation (c.989 + 1G >A) in ARR3, one missense mutation (c.995C > A, p.Thr332Lys) in NDUFAF7 and one novel frameshift mutation (c.726dupA, p.Arg243fs*140) in SLC39A5. The potential pathogenic group included two missense mutations (c.3266A > G, p.Tyr1089Cys; c.913G > A, p.Glu305Lys) in ZNF644 and one missense mutation (c.960T > A, p.His320Gln) in NDUFAF7. Sequence changes were confirmed by Sanger sequencing; all had an allele frequency <0.01 in the 1000G, EVS, ExAC and gnomAD databases. Additionally, both the pathogenic and potentially pathogenic mutations were predicted to be damaging by SIFT, Polyphen-2, PROVEAN, MutationTaster2, CADD and REVEL except the p.Tyr1089Cys and p.Glu305Lys changes were predicted to be neutral by PROVEAN.

Conclusion: Our research provides more evidence to support the hypothesis that mutations in ARR3, SLC39A5 and NDUFAF7 are disease-causing genes for eo-HM and broadens the eo-HM mutation spectrum among different ethnic groups. It also deepens understanding of the contributions of ARR3, SLC39A5, and NDUFAF7 to eo-HM.

Keywords: ARR3; NDUFAF7; SLC39A5; early-onset high myopia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Mutation*
  • Myopia / genetics*
  • Transcription Factors / genetics


  • Transcription Factors