New ZNF644 mutations identified in patients with high myopia.

ABSTRACT

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>Gp.T401A, c.2867C>Gp.T956S, c.3833A>Gp.E1278G), one is synonymous (c.2565A>Gp.T855T), and one (c.-219C>A) is located in the 5' UTR. Functional prediction indicates that c.3833A>Gp.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.