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T. Rezaie, A. Child, S. Popinchalk, T. Krupin, R. Ritch, J. Liebmann, E. Ilitchev, R. Crick, M. Sarfarazi; Large–Scale Sequencing of the Optineurin Gene in Familial and Sporadic Cases With Primary Open–Angle Glaucoma . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1306.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Previously, we showed that mutations in the Optineurin (OPTN) gene are involved in the etiology of adult–onset primary open–angle glaucoma (POAG) linked to the GLC1E locus on 10p14 (Science 295:1077–1079; 2002). The purpose of this study was to screen the entire coding regions of OPTN in a cohort of familial and sporadic patients with high– or low–pressure glaucoma by direct DNA sequencing. Methods: Genomic DNA from 650 unrelated POAG subjects were used to screen for OPTN mutations. Clinical diagnosis of all the affected subjects was confirmed prior to this study. All the 13 coding exons of OPTN gene and their intron–exon boundaries were PCR amplified and screened for potential sequence alteration by direct DNA sequencing. Results: So far, a total of 36 sequence alterations have been observed in the Optineurin gene. Of these, 11 DNA variations are considered disease–causing mutations (i.e., P16A, Q42H, E50K, K66R, E92V, c.691_692insAG, H228Y, E293A, E322K, A466S, R545Q); another 10 were amino acid polymorphisms (i.e., T34T, L41L, R83R, M98K, A134A, E163E, Q245Q, P292P, S297S, S321S) and the remaining 15 were intronic single nucleotide polymorphisms (i.e., IVS5+38T>G, IVS6–5T>C, IVS7–10T>C, IVS7+24G>A, IVS8–53T>C, IVS8–21C>T, IVS8+20G>A, IVS9+3G>A, IVS10–5C>T, IVS11–86G>T, IVS11–44G>T, IVS14–49T>C, IVS15–3C>T, IVS15+9C>G, IVS15+10G>A). The exact role of observed sequence alterations in the etiology of POAG is currently being investigated further. Conclusions: Our findings provide additional evidences for involvement of Optineurin mutations in both low– and high–pressure glaucoma. Supported by EY–09947, EY–014959 and M01RR–06192.
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