Lack of association of mutations in optineurin with disease in patients with adult-onset primary open-angle glaucoma.
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.
Wiggs
Janey L
JL
Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Auguste
Josette
J
Allingham
R Rand
RR
Flor
Jason D
JD
Pericak-Vance
Margaret A
MA
Rogers
Kathryn
K
LaRocque
Karen R
KR
Graham
Felicia L
FL
Broomer
Bob
B
Del Bono
Elizabeth
E
Haines
Jonathan L
JL
Hauser
Michael
M
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
D018797:Cell Cycle Proteins; D005136:Eye Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA