title: Unique Variants in OPN1LW Cause Both Syndromic and Nonsyndromic X-Linked High Myopia Mapped to MYP1.
abstract: OBJECTIVE
  MYP1 is a locus for X-linked syndromic and nonsyndromic high myopia. Recently, unique haplotypes in OPN1LW were found to be responsible for X-linked syndromic high myopia mapped to MYP1. The current study is to test if such variants in OPN1LW are also responsible for X-linked nonsyndromic high myopia mapped to MYP1.
  
  
  METHODS
  The proband of the family previously mapped to MYP1 was initially analyzed using whole-exome sequencing and whole-genome sequencing. Additional probands with early-onset high myopia were analyzed using whole-exome sequencing. Variants in OPN1LW were selected and confirmed by Sanger sequencing. Long-range and second PCR were used to determine the haplotype and the first gene of the red-green gene array. Candidate variants were further validated in family members and controls.
  
  
  RESULTS
  The unique LVAVA haplotype in OPN1LW was detected in the family with X-linked nonsyndromic high myopia mapped to MYP1. In addition, this haplotype and a novel frameshift mutation (c.617_620dup, p.Phe208Argfs*51) in OPN1LW were detected in two other families with X-linked high myopia. The unique haplotype cosegregated with high myopia in the two families, with a maximum LOD score of 3.34 and 2.31 at θ = 0. OPN1LW with the variants in these families was the first gene in the red-green gene array and was not present in 247 male controls. Reevaluation of the clinical data in both families with the unique haplotype suggested nonsyndromic high myopia.
  
  
  CONCLUSIONS
  Our study confirms the findings that unique variants in OPN1LW are responsible for both syndromic and nonsyndromic X-linked high myopia mapped to MYP1.
authors.affiliation: State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Gao
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xueshan
authors.initials: X
authors.lastname: Xiao
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jia
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: Guo
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yin
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D044466:Asian People / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D016368:Frameshift Mutation; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009216:Myopia / Q000235:genetics*; D047728:Myopia, Degenerative / Q000235:genetics*; D010375:Pedigree; D017299:Rod Opsins / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D017299:Rod Opsins; C095855:long-wavelength opsin