title: Adult-onset primary open-angle glaucoma caused by mutations in optineurin.
abstract: Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.
authors.affiliation: Molecular Ophthalmic Genetics Laboratory, Surgical Research Center, Department of Surgery, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Tayebeh
authors.initials: T
authors.lastname: Rezaie
authors.forename: Anne
authors.initials: A
authors.lastname: Child
authors.forename: Roger
authors.initials: R
authors.lastname: Hitchings
authors.forename: Glen
authors.initials: G
authors.lastname: Brice
authors.forename: Lauri
authors.initials: L
authors.lastname: Miller
authors.forename: Miguel
authors.initials: M
authors.lastname: Coca-Prados
authors.forename: Elise
authors.initials: E
authors.lastname: Héon
authors.forename: Theodore
authors.initials: T
authors.lastname: Krupin
authors.forename: Robert
authors.initials: R
authors.lastname: Ritch
authors.forename: Donald
authors.initials: D
authors.lastname: Kreutzer
authors.forename: R Pitts
authors.initials: RP
authors.lastname: Crick
authors.forename: Mansoor
authors.initials: M
authors.lastname: Sarfarazi
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002924:Ciliary Body / Q000378:metabolism; D005091:Exons; D005136:Eye Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D005260:Female; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006056:Golgi Apparatus / Q000737:chemistry; D006579:Heterozygote; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D009798:Ocular Hypertension / Q000235:genetics; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D012160:Retina / Q000378:metabolism; D014129:Trabecular Meshwork / Q000378:metabolism; D035582:Transcription Factor TFIIIA; D016335:Zinc Fingers
chemical_list: D018797:Cell Cycle Proteins; D005136:Eye Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA