title: Evaluation of NTF4 as a causative gene for primary open-angle glaucoma.
abstract: OBJECTIVE
  The neurotrophin-4 (NTF4) gene has been recently implicated in primary open-angle glaucoma (POAG). In this study, we investigated the implication of NTF4 in POAG among three Chinese cohorts.
  
  
  METHODS
  The coding regions and exon-intron boundaries of NTF4 was sequenced in 950 unrelated Chinese subjects, including a Hong Kong cohort of 390 patients and 230 controls, a Shantou cohort of 130 patients, and a Beijing cohort of 200 patients. Constructs carrying the detected variants were generated using site-directed mutagenesis and transfected into HeLa cells, followed by solubility and migration analyses.
  
  
  RESULTS
  Three variants were identified. p.Pro151Pro was detected in three POAG patients and one control subject. Two novel missense variants, p.Gly157Ala and p.Ala182Val, were identified each in one POAG patient from the Hong Kong cohort, but not in controls. Functional assays showed that the p.Gly157Ala mutant protein was less soluble in Triton X-100, and that migration of HeLa cells transfected with either mutant construct was less than cells transfected with the wildtype.
  
  
  CONCLUSIONS
  The NTF4 variants p.Gly157Ala and p.Ala182Val have been shown to be functional mutations, occurring in 2 of a total of 720 Chinese POAG patients. NTF4 is functionally related to POAG pathogenesis but its mutation frequency is low. Therefore, NTF4 does not have a major contribution in the molecular genetics of POAG.
authors: Department of Ophthalmology and Visual Sciences, the Chinese University of Hong Kong, Hong Kong, China.
authors: Li Jia
authors: LJ
authors: Chen
authors: Tsz Kin
authors: TK
authors: Ng
authors: Alex H
authors: AH
authors: Fan
authors: Dexter Y L
authors: DY
authors: Leung
authors: Mingzhi
authors: M
authors: Zhang
authors: Ningli
authors: N
authors: Wang
authors: Yuqian
authors: Y
authors: Zheng
authors: Xiao Ying
authors: XY
authors: Liang
authors: Sylvia W Y
authors: SW
authors: Chiang
authors: Pancy O S
authors: PO
authors: Tam
authors: Chi Pui
authors: CP
authors: Pang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002465:Cell Movement; D002648:Child; D015331:Cohort Studies; D005091:Exons; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D009414:Nerve Growth Factors / Q000235:genetics*; D016366:Open Reading Frames; D014162:Transfection
chemical_list: D009414:Nerve Growth Factors; C073922:neurotrophin 4