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Abstract #5947 Published in IGR 2-2
Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma
Shimizu S; Lichter PR; Johnson AT; Zhou Z; Higashi M; Gottfredsdottir M; Othman M; Moroi SE; Rozsa FW; Schertzer RMAmerican Journal of Ophthalmology 2000; 130: 165-177
PURPOSE: To screen a population with primary open-angle glaucoma for mutations in the gene that encodes the trabecular meshwork inducible glucocorticoid response protein (TIGR), also known as myocilin (MYOC). METHODS: Ophthalmological information was collected for study subjects with primary open-angle glaucoma (POAG) and their relatives. Mutation screening of 74 POAG probands was conducted by sequencing TIGR/MYOC coding sequence and splice sites. RESULTS: In 23 families, the authors detected 13 nonsynonymous sequence changes, nine of which appear to be mutations likely to cause or contribute to POAG. Two mutations, Arg272Gly and Ile499Ser, and one nonsynonymous sequence variant, Asn57Asp, are novel. The authors found mutations in nine of 25 juvenile glaucoma probands (36%) and two of 49 adult-onset glaucoma probands (4%). Age classification of families rather than individual probands revealed mutations in three of nine families with strictly juvenile POAG (33%), and no mutations in 39 families with strictly adult-onset POAG (0%). In families with mixed-onset POAG containing both juvenile POAG and adult-onset POAG cases, the authors found mutations in eight of 26 families (31%). CONCLUSIONS: These data suggest that Gly252Arg, Arg272Gly, Glu323Lys, Gln368STOP, Pro370Leu, Thr377Met, Val426Phe, Ile477Asn, and Ile499Ser, are likely to play roles that cause or contribute to the etiology of autosomal dominant POAG. The finding of more TIGR/MYOC mutations in families with mixed-onset POAG than in families with strictly adult-onset POAG implies that the presence of relatives with juvenile POAG in a family could be used as a basis for identifying a subset of the population with adult-onset POAG with a higher prevalence of TIGR/MYOC mutations. To address this issue, and to refine estimations of mutation prevalence in these age-defined subpopulations, the prospective study of a larger population ascertained entirely through adult-onset POAG probands will be needed.
Dr. S. Shimizu, Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, MI, USA
Classification:
1.2 Population genetics (Part of: 1 General aspects)
