title: Lack of association of mutations in optineurin with disease in patients with adult-onset primary open-angle glaucoma.
abstract: OBJECTIVE
  To determine whether mutations in the optineurin gene contribute to susceptibility to adult-onset primary open-angle glaucoma.
  
  
  METHODS
  The optineurin gene was screened in 86 probands with adult-onset primary open-angle glaucoma and in 80 age-matched control subjects. Exons 4 and 5, containing the recurrent mutations identified in patients with normal-tension glaucoma, were sequenced in all individuals studied, while the remaining exons were screened for DNA sequence variants with denaturing high-performance liquid chromatography.
  
  
  RESULTS
  The recurrent mutation, Met98Lys, previously found to be associated with an increased risk of disease was found in 8 (9%) of 86 probands. We also found the Met98Lys mutation in 10% of individuals from a control population of similar age, sex, and ethnicity. Consistent segregation of the mutation with the disease was not demonstrated in any of the 8 families. No other DNA changes altering the amino acid structure of the protein were found.
  
  
  CONCLUSIONS
  The mutations in the optineurin gene associated with normal-tension glaucoma are not associated with adult-onset primary open-angle glaucoma in this patient population. Clinical Relevance Genetic abnormalities that render the optic nerve susceptible to degeneration are excellent candidates for genetic factors that could contribute to adult-onset primary open-angle glaucoma. Mutations in optineurin have been associated with normal-tension glaucoma, but are not associated with disease in patients with adult-onset primary open-angle glaucoma. This result may indicate that normal-tension glaucoma is not necessarily part of the phenotypic spectrum of adult open-angle glaucoma.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
authors.forename: Josette
authors.initials: J
authors.lastname: Auguste
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
authors.forename: Jason D
authors.initials: JD
authors.lastname: Flor
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.forename: Kathryn
authors.initials: K
authors.lastname: Rogers
authors.forename: Karen R
authors.initials: KR
authors.lastname: LaRocque
authors.forename: Felicia L
authors.initials: FL
authors.lastname: Graham
authors.forename: Bob
authors.initials: B
authors.lastname: Broomer
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Del Bono
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Michael
authors.initials: M
authors.lastname: Hauser
mesh_terms: D000368:Aged; D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D026901:Membrane Transport Proteins; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D017422:Sequence Analysis, DNA; D035582:Transcription Factor TFIIIA
chemical_list: D018797:Cell Cycle Proteins; D005136:Eye Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA