Study Of A U.S. Caucasian Cohort Supports The Role Of Znf644 In High-grade Myopia Susceptibility

Abstract

Purpose: : Myopia, or nearsightedness, is highly prevalent in urban Asia and is considered a significant public health issue globally. High-grade myopia predisposes individuals to myopic maculopathy, premature cataracts, retinal detachment, and glaucoma. A recent study identified zinc finger protein 644 isoform 1 (ZNF644) sequence variants in a Chinese high-grade myopia [< -10.00 diopters (D)] case-control study. We screened for ZNF644 sequence variants in a Caucasian U.S. case-control study.

Methods: : DNA samples from a cohort of 131 adult individuals with high-grade myopia were screened for ZNF644 coding sequence variants. A refractive error of <-6.00 D in at least one eye was defined as affected. All ZNF644 coding and intron/exon boundaries were screened using Sanger sequencing. Allele frequencies of detected sequence variants were assessed by screening 672 ethnically matched non-myopic controls.

Results: : Sequencing did not reveal any previously reported causal mutation. However, our analysis identified two novel non-synonymous sequence variants (T242M, E274M) in two cases. These variants were absent from all controls. A known rare coding sequence variant (rs12117237, K707E) was present in six additional cases, but was also discovered in five controls.

Conclusions: : Our study identified two novel sequence variant mutations in ZNF644 for high-grade myopia in a U.S. Caucasian cohort. Our results suggest that ZNF644 may also play a role in high-grade myopia development in Caucasians.

Keywords: myopia • gene screening