New ZNF644 mutations identified in patients with high myopia

PURPOSE Myopia, or near-sightedness, is one of the most common human visual impairments worldwide, and high myopia is one of the leading causes of blindness. In this study, we investigated the mutation spectrum of ZNF644, a causative gene for autosomal dominant high myopia, in a high-myopia cohort from a Chinese population. METHODS DNA was isolated with the standard proteinase K digestion and phenol-chloroform method from a case cohort of 186 subjects diagnosed with high myopia (spherical refractive error equal or less than -6.00 diopters). Sanger sequencing was performed to find potential mutations in all coding exons, flanking splicing sites, and untranslated regions (UTRs) of ZNF644 (NM_201269). Identified novel variants were further screened in 526 ethnically matched normal controls. Functional prediction and conservation analysis were performed using ANNOVAR. RESULTS Five novel variants were identified. Three are missense (c.1201A>G:p.T401A, c.2867C>G:p.T956S, c.3833A>G:p.E1278G), one is synonymous (c.2565A>G:p.T855T), and one (c.-219C>A) is located in the 5' UTR. Functional prediction indicates that c.3833A>G:p.E1278G was predicted to be damaging by SIFT and Polyphen2. Conservation analysis using PhyloP and GERP++ indicate all of the missense variants are highly conserved. None of these novel mutations was identified in 526 normal controls. CONCLUSIONS ZNF644 is associated with high myopia in a cohort from a Chinese population. ZNF644 mutations have a minor contribution to the genetic etiology of high myopia.