Adult-onset primary open-angle glaucoma caused by mutations in optineurin

Science. 2002 Feb 8;295(5557):1077-9. doi: 10.1126/science.1066901.

Abstract

Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Alternative Splicing
  • Amino Acid Sequence
  • Brain / metabolism
  • Cell Cycle Proteins
  • Chromosome Mapping
  • Chromosomes, Human, Pair 10 / genetics
  • Ciliary Body / metabolism
  • Exons
  • Eye Proteins / analysis
  • Eye Proteins / chemistry
  • Eye Proteins / genetics*
  • Eye Proteins / physiology
  • Female
  • Glaucoma, Open-Angle / genetics*
  • Golgi Apparatus / chemistry
  • Heterozygote
  • Humans
  • Intraocular Pressure
  • Male
  • Membrane Transport Proteins
  • Middle Aged
  • Mutation*
  • Mutation, Missense*
  • Nerve Tissue Proteins / analysis
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology
  • Ocular Hypertension / genetics
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • Retina / metabolism
  • Trabecular Meshwork / metabolism
  • Transcription Factor TFIIIA*
  • Zinc Fingers

Substances

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