title: Age-dependent prevalence of mutations at the GLC1A locus in primary open-angle glaucoma.
abstract: OBJECTIVE
  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
  Ophthalmologic information was collected for study subjects with primary open-angle glaucoma and their relatives. Mutation screening of 74 primary open-angle glaucoma probands was conducted by sequencing TIGR/MYOC coding sequence and splice sites.
  
  
  RESULTS
  In 23 families we detected 13 nonsynonymous sequence changes, nine of which appear to be mutations likely to cause or contribute to primary open-angle glaucoma. Two mutations, Arg272Gly and Ile499Ser, and one nonsynonymous sequence variant, Asn57Asp, are novel. We 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 primary open-angle glaucoma (33%), and no mutations in 39 families with strictly adult-onset primary open-angle glaucoma (0%). In families with mixed-onset primary open-angle glaucoma containing both juvenile primary open-angle glaucoma and adult-onset primary open-angle glaucoma cases, we found mutations in eight of 26 families (31%).
  
  
  CONCLUSIONS
  Our 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 primary open-angle glaucoma. Our finding of more TIGR/MYOC mutations in families with mixed-onset primary open-angle glaucoma than in the families with strictly adult-onset primary open-angle glaucoma implies that the presence of relatives with juvenile primary open-angle glaucoma in a family could be used as a basis for identifying a subset of the population with adult-onset primary open-angle glaucoma with higher prevalence of TIGR/MYOC mutations. To address this issue, and to refine estimations of mutation prevalence in these age-defined subpopulations, prospective study of a larger population ascertained entirely through adult-onset primary open-angle glaucoma probands will be needed.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, Michigan 48105, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shimizu
authors.forename: P R
authors.initials: PR
authors.lastname: Lichter
authors.forename: A T
authors.initials: AT
authors.lastname: Johnson
authors.forename: Z
authors.initials: Z
authors.lastname: Zhou
authors.forename: M
authors.initials: M
authors.lastname: Higashi
authors.forename: M
authors.initials: M
authors.lastname: Gottfredsdottir
authors.forename: M
authors.initials: M
authors.lastname: Othman
authors.forename: S E
authors.initials: SE
authors.lastname: Moroi
authors.forename: F W
authors.initials: FW
authors.lastname: Rozsa
authors.forename: R M
authors.initials: RM
authors.lastname: Schertzer
authors.forename: M S
authors.initials: MS
authors.lastname: Clarke
authors.forename: A L
authors.initials: AL
authors.lastname: Schwartz
authors.forename: C A
authors.initials: CA
authors.lastname: Downs
authors.forename: D
authors.initials: D
authors.lastname: Vollrath
authors.forename: J E
authors.initials: JE
authors.lastname: Richards
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002648:Child; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D015995:Prevalence; D014129:Trabecular Meshwork / Q000473:pathology; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D017931:DNA Primers; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin