title: Identification of a novel mutation in the NTF4 gene that causes primary open-angle glaucoma in a Chinese population.
abstract: OBJECTIVE
  Neurotrophin-4 protein (NT-4) plays a role in the protection of retinal ganglion cells by activating tyrosine kinase B (TrkB) receptors. A recent study identified mutations within the neurotrophin-4 (NTF4) gene to account for 1.7% of primary open-angle glaucoma (POAG) in Europeans. The aim of this study was to investigate the frequency of NTF4 mutations in Chinese POAG patients.
  
  
  METHODS
  One hundred-seventy-four Chinese subjects with POAG and 91 normal Chinese subjects were recruited. POAG was defined by the presence of glaucomatous optic neuropathy, open angles on gonioscopy, and absence of secondary causes of glaucoma. The single coding exon of NTF4 was PCR amplified and subjected to bidirectional sequencing in all subjects.
  
  
  RESULTS
  The mean age of POAG patients was 66.0+/-13.0 years (range 25-96 years) and that of controls was 67.1+/-4.6 years (range 60-85 years). We identified a novel NTF4 missense mutation substituting leucine by serine at codon 113 (Leu113Ser) caused by a c.338T>C mutation in a single patient with unilateral POAG, who presented with a baseline intraocular pressure of 25 mmHg, a vertical cup-to-disc ratio of 0.9 and an inferior hemifield defect in the affected eye. Structural analysis indicated that the Leu113Ser mutation is likely to alter the NT-4 protein structure near the TrkB binding site and disrupts the formation of the NT-4-TrkB complex required for the activation of TrkB.
  
  
  CONCLUSIONS
  Identification of a single mutation in our study suggests that NTF4 mutations are a rare cause of POAG (0.6%, 95%CI 0.02%-3.16%) in Chinese people.
authors.affiliation: Singapore Eye Research Institute, 11 Third Hospital Avenue, Singapore. eranga.n.v@seri.com.sg
authors.forename: Eranga N
authors.initials: EN
authors.lastname: Vithana
authors.forename: Monisha E
authors.initials: ME
authors.lastname: Nongpiur
authors.forename: Divya
authors.initials: D
authors.lastname: Venkataraman
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Chan
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Mavinahalli
authors.forename: Tin
authors.initials: T
authors.lastname: Aung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics*; D017433:Protein Structure, Secondary
chemical_list: D009414:Nerve Growth Factors; C073922:neurotrophin 4
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