title: Study of a US cohort supports the role of ZNF644 and high-grade myopia susceptibility.
abstract: OBJECTIVE
  Myopia, or nearsightedness, is highly prevalent in Asian countries and is considered a serious public health issue globally. High-grade myopia can predispose individuals to myopic maculopathy, premature cataracts, retinal detachment, and glaucoma. A recent study implicated zinc finger protein 644 isoform 1 (ZNF644) variants with non-syndromic high-grade myopia in a Chinese-Asian population. Herein we focused on investigating the role for ZNF644 variants in high-grade myopia in a United States (US) cohort.
  
  
  METHODS
  DNA from a case cohort of 131 subject participants diagnosed with high-grade myopia was screened for ZNF644 variants. Spherical refractive error of -≤-6.00 diopters (D) in at least one eye was defined as affected. All coding, intron/exon boundaries were screened using Sanger sequencing. Single nucleotide allele frequencies were determined by screening 672 ethnically matched controls.
  
  
  RESULTS
  Sequencing analysis did not detect previously reported mutations. However, our analysis identified 2 novel single nucleotide variants (c.725C>T, c.821A>T) in 2 high-grade myopia individuals- one Caucasian and one African American, respectively. These variants were not found in normal controls. A rare variant - dbsSNP132 (rs12117237→c.2119A>G) - with a minor allele frequency of 0.2% was present in 6 additional cases, but was also present in 5 controls.
  
  
  CONCLUSIONS
  Our study has identified two novel variants in ZNF644 associated with high-grade myopia in a US cohort. Our results suggest that ZNF644 may play a role in myopia development.
authors.affiliation: The Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Khanh-Nhat
authors.initials: KN
authors.lastname: Tran-Viet
authors.forename: Elizabeth
authors.initials: E
authors.lastname: St Germain
authors.forename: Vincent
authors.initials: V
authors.lastname: Soler
authors.forename: Caldwell
authors.initials: C
authors.lastname: Powell
authors.forename: Sing-Hui
authors.initials: SH
authors.lastname: Lim
authors.forename: Thomas
authors.initials: T
authors.lastname: Klemm
authors.forename: Seang Mei
authors.initials: SM
authors.lastname: Saw
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
mesh_terms: D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005091:Exons; D005123:Eye / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009216:Myopia / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases; D014481:United States; D044465:White People / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*; D001741:Black or African American
chemical_list: C552601:CBLL2 protein, human; D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases