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Janey L. Wiggs, MD, PhD; Josette Auguste, BA; R. Rand Allingham, MD; Jason D. Flor, BA; Margaret A. Pericak-Vance, PhD; Kathryn Rogers, BA; Karen R. LaRocque, BA; Felicia L. Graham, MA; Bob Broomer, BA; Elizabeth Del Bono, MPH; Jonathan L. Haines, PhD; Michael Hauser, PhD

Arch Ophthalmol. 2003;121:1181-1183.

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.

Conclusion  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.

From the Department of Ophthalmology, Harvard Medical School, Boston, Mass (Dr Wiggs and Mss Auguste, Rogers, and Del Bono); Department of Ophthalmology (Dr Allingham and Mr Broomer) and Center for Human Genetics (Mr Flor; Drs Pericak-Vance and Hauser; and Mss LaRocque and Graham), Duke School of Medicine, Durham, NC; and Program in Human Genetics, Vanderbilt School of Medicine, Nashville, Tenn (Dr Haines). The authors have no relevant financial interest in this article.

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