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Abstract #59289 Published in IGR 16-3
Copy Number Variations of TBK1 in Australian Patients With Primary Open-Angle Glaucoma
Awadalla MS; Fingert JH; Roos BE; Chen S; Holmes R; Graham SL; Chehade M; Galanopolous A; Ridge B; Souzeau E; Zhou T; Siggs OM; Hewitt AW; Mackey DA; Burdon KP; Craig JEAmerican Journal of Ophthalmology 2015; 159: 124-130.e1
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.
Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, Australia. Electronic address: mona.awadalla@flinders.edu.au.
Full articleClassification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
