Copy number variations of TBK1 in Australian patients with primary open-angle glaucoma

Mona Awadalla, John Fingert, Benjamin Roos, S Chen, Richard Holmes, Stuart Graham, Mark Chehade, Anna Galanopolous, Bronwyn Ridge, Emmanuelle Souzeau, Tiger Zhou, Owen Siggs, A W Hewitt, D Mackey, Kathryn Burdon, Jamie Craig

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    42 Citations (Scopus)

    Abstract

    Purpose To investigate the presence of TBK1 copy number variations in a large, well-characterized Australian cohort of patients with glaucoma comprising both normal-tension glaucoma and high-tension glaucoma cases. Design A retrospective cohort study. Methods DNA samples from patients with normal-tension glaucoma and high-tension glaucoma and unaffected controls were screened for TBK1 copy number variations using real-time quantitative polymerase chain reaction. Samples with additional copies of the TBK1 gene were further tested using custom comparative genomic hybridization arrays. Results Four out of 334 normal-tension glaucoma cases (1.2%) were found to carry TBK1 copy number variations using quantitative polymerase chain reaction. One extra dose of the TBK1 gene (duplication) was detected in 3 normal-tension glaucoma patients, while 2 extra doses of the gene (triplication) were detected in a fourth normal-tension glaucoma patient. The results were further confirmed by custom comparative genomic hybridization arrays. Further, the TBK1 copy number variation segregated with normal-tension glaucoma in the family members of the probands, showing an autosomal dominant pattern of inheritance. No TBK1 copy number variations were detected in 1045 Australian patients with high-tension glaucoma or in 254 unaffected controls. Conclusion We report the presence of TBK1 copy number variations in our Australian normal-tension glaucoma cohort, including the first example of more than 1 extra copy of this gene in glaucoma patients (gene triplication). These results confirm TBK1 to be an important cause of normal-tension glaucoma, but do not suggest common involvement in high-tension glaucoma.

    Original languageEnglish
    Pages (from-to)124-130.e1
    Number of pages7
    JournalAmerican Journal of Ophthalmology
    Volume159
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2015

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