Different optineurin mutation pattern in primary open-angle glaucoma

Invest Ophthalmol Vis Sci. 2003 Sep;44(9):3880-4. doi: 10.1167/iovs.02-0693.


Purpose: The optineurin gene (OPTN) is the second gene besides MYOC in which mutations have been identified to be associated with primary open-angle glaucoma (POAG). In this study, sequence alterations in the OPTN gene associated with POAG in Chinese subjects were investigated.

Methods: All the coding exons of OPTN were screened, including the intron-exon boundaries, for sequence alterations in a Chinese sample of 119 sporadic patients with POAG and 126 unrelated control subjects by polymerase chain reaction-conformation-sensitive gel electrophoresis and DNA sequencing.

Results: Sixteen sequence changes were identified: 3 had been reported (T34T, M98K, and R545Q) and 13 were novel (T49T, E103D, V148V, P199P, T202T, H486R, IVS6-5T-->C, IVS6-10G-->A, IVS7+24G-->A, IVS8+20G-->A, IVS13+21C-->G, IVS15+10G-->A, and IVS15-48C-->A). Among them, only E103D, H486R, V148V, and IVS13+21C-->G were found exclusively in patients with POAG, whereas P199P, T202T, and IVS8+20G-->A were present only in control subjects. The genotype of IVS7+24G-->A showed a significant association with POAG (P = 0.02, Fisher two-tailed exact test) and with and increased cup-to-disc ratio in these patients (P = 0.005, Mann-Whitney test).

Conclusions: The findings in the current study enrich the evidence on the OPTN gene as a causative gene for POAG and suggest a different mutation pattern of OPTN in Chinese than in whites. The wide spectrum of putative mutations detected in this study suggests that both structural and functional disruptions in OPTN may contribute to the pathogenesis of glaucoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People / genetics
  • Cell Cycle Proteins
  • Child
  • DNA Mutational Analysis
  • Female
  • Genotype
  • Glaucoma, Open-Angle / ethnology
  • Glaucoma, Open-Angle / genetics*
  • Hong Kong / epidemiology
  • Humans
  • Male
  • Membrane Transport Proteins
  • Middle Aged
  • Mutation*
  • Phenotype
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Transcription Factor TFIIIA / genetics*


  • Cell Cycle Proteins
  • Membrane Transport Proteins
  • OPTN protein, human
  • Transcription Factor TFIIIA