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.

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.

Representative pedigrees showing the segregation of disease and the Met98Lys DNA sequence variant genotypes. M/M is homozygous for methionine at codon 98, while M/K is heterozygous for the methionine/lysine at codon 98. Square indicates male; circle, female; diagonal line, deceased; solid symbol, affected individual; and question mark, unknown allele.