Tank-Binding Kinase 1 (TBK1) Gene and Open-Angle Glaucomas (An American Ophthalmological Society Thesis)

Trans Am Ophthalmol Soc. 2016 Aug:114:T6.

Abstract

Purpose: To investigate the role of TANK-binding kinase 1 (TBK1) gene copy-number variations (ie, gene duplications and triplications) in the pathophysiology of various open-angle glaucomas.

Methods: In previous studies, we discovered that copy-number variations in the TBK1 gene are associated with normal-tension glaucoma. Here, we investigated the prevalence of copy-number variations in cohorts of patients with other open-angle glaucomas-juvenile-onset open-angle glaucoma (n=30), pigmentary glaucoma (n=209), exfoliation glaucoma (n=225), and steroid-induced glaucoma (n=79)-using a quantitative polymerase chain reaction assay.

Results: No TBK1 gene copy-number variations were detected in patients with juvenile-onset open-angle glaucoma, pigmentary glaucoma, or steroid-induced glaucoma. A TBK1 gene duplication was detected in one (0.44%) of the 225 exfoliation glaucoma patients.

Conclusions: TBK1 gene copy-number variations (gene duplications and triplications) have been previously associated with normal-tension glaucoma. An exploration of other open-angle glaucomas detected a TBK1 copy-number variation in a patient with exfoliation glaucoma, which is the first example of a TBK1 mutation in a glaucoma patient with a diagnosis other than normal-tension glaucoma. A broader phenotypic range may be associated with TBK1 copy-number variations, although mutations in this gene are most often detected in patients with normal-tension glaucoma.

MeSH terms

  • Aged
  • Case-Control Studies
  • DNA / genetics*
  • DNA Mutational Analysis
  • Female
  • Follow-Up Studies
  • Gene Dosage
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / metabolism
  • Humans
  • Male
  • Mutation*
  • Ophthalmology
  • Prospective Studies
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Societies, Medical
  • United States

Substances

  • DNA
  • Protein Serine-Threonine Kinases
  • TBK1 protein, human