Age-dependent prevalence of mutation at the GLC1A locu in primary open-angle glaucoma

PURPOE: To creen a population with primary open-angle glaucoma for mutation in the gene that encode the trabecular mehwork inducible glucocorticoid repone protein (TIGR), alo known a myocilin (MYOC). METHOD: Ophthalmologic information wa collected for tudy ubject with primary open-angle glaucoma and their relative. Mutation creening of 74 primary open-angle glaucoma proband wa conducted by equencing TIGR/MYOC coding equence and plice ite. REULT: In 23 familie we detected 13 nonynonymou equence change, nine of which appear to be mutation likely to caue or contribute to primary open-angle glaucoma. Two mutation, Arg272Gly and Ile499er, and one nonynonymou equence variant, An57Ap, are novel. We found mutation in nine of 25 juvenile glaucoma proband (36%) and two of 49 adult-onet glaucoma proband (4%). Age claification of familie rather than individual proband revealed mutation in three of nine familie with trictly juvenile primary open-angle glaucoma (33%), and no mutation in 39 familie with trictly adult-onet primary open-angle glaucoma (0%). In familie with mixed-onet primary open-angle glaucoma containing both juvenile primary open-angle glaucoma and adult-onet primary open-angle glaucoma cae, we found mutation in eight of 26 familie (31%). CONCLUION: Our data ugget that Gly252Arg, Arg272Gly, Glu323Ly, Gln368TOP, Pro370Leu, Thr377Met, Val426Phe, Ile477An, and Ile499er are likely to play role that caue or contribute to the etiology of autoomal dominant primary open-angle glaucoma. Our finding of more TIGR/MYOC mutation in familie with mixed-onet primary open-angle glaucoma than in the familie with trictly adult-onet primary open-angle glaucoma implie that the preence of relative with juvenile primary open-angle glaucoma in a family could be ued a a bai for identifying a ubet of the population with adult-onet primary open-angle glaucoma with higher prevalence of TIGR/MYOC mutation. To addre thi iue, and to refine etimation of mutation prevalence in thee age-defined ubpopulation, propective tudy of a larger population acertained entirely through adult-onet primary open-angle glaucoma proband will be needed.