title: Variants of the myocilin gene in Japanese patients with normal-tension glaucoma.
abstract: Myocilin (MYOC) mutations are associated with juvenile- and adult-onset primary open-angle glaucoma (POAG). The purpose of this study was to determine whether MYOC gene mutations are associated with normal-tension glaucoma (NTG). The prevalence of MYOC mutations was determined in 80 Japanese NTG patients and 100 control subjects. In addition, the expression of mutant MYOC was determined by transforming COS-1 cells with five myocilin variants (R158Q, D208E, I360N, A363T, and I477S) and examining whether myocilin was present in the cultured cells and/or the culture medium by western blotting. Six different nucleotide sequence variants, R46Stop, R76K, R158Q, D208E, A488A, and one in the 3' non-coding region, were identified in 80 NTG patients. Variants in codon 46 (R46Stop), codon 158 (R158Q), and codon 488 (A488A) were not found in the 100 normal controls. The frequency of other sequence changes (R76K, D208E, and 3' non-coding) in NTG patients did not differ significantly from the frequencies in the control subjects. COS-1 cells transfected with the wild type, R158Q, or D208E variants secreted myocilin into the culture medium. On the other hand, the detected myocilin was significantly reduced in the medium of cells transfected with the I360N, A363T, or I477S variants that were previously identified as mutations for POAG. Definitive evidence of MYOC variants associated with NTG was not found.
authors.affiliation: National Institute of Sensory Organs, National Tokyo Medical Center, Higashigaoka, Tokyo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Izumi
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Mashima
authors.forename: Minoru
authors.initials: M
authors.lastname: Obazawa
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohtake
authors.forename: Tomihiko
authors.initials: T
authors.lastname: Tanino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Oguchi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwata
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D012333:RNA, Messenger; D000099179:Myocilin