title: New ZNF644 mutations identified in patients with high myopia.
abstract: OBJECTIVE
  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.
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China ; School of Life Science, Central South University, Changsha, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Xiang
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Tianyun
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Tong
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China ; School of Life Science, Central South University, Changsha, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Anran
authors.initials: A
authors.lastname: Wan
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xia
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tian
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Shen
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China.
authors.forename: Xinzhang
authors.initials: X
authors.lastname: Cai
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Jin
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China ; School of Life Science, Central South University, Changsha, China ; Key Laboratory of Medical Information Research (Central South University), Changsha, Hunan, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xia
authors.affiliation: The State Key Laboratory of Medical Genetics, Central South University, Changsha, China ; School of Life Science, Central South University, Changsha, China.
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009216:Myopia / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012030:Refractive Errors / Q000150:complications / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
chemical_list: D014157:Transcription Factors; C573234:ZNF644 protein, human