title: Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma.
abstract: Primary open-angle glaucoma (POAG) is a highly prevalent cause of irreversible blindness which associates cupping of the optic disc and alteration of the visual field, elevation of intraocular pressure being a major risk factor. Provided diagnosis is made at an early stage, treatments are available to prevent visual impairment. A locus, GLC1A, has been mapped on chromosome 1q23-q25 in several families affected with juvenile-onset POAG (JOAG) and also in some families affected with juvenile and middle-age onset POAG. Recently, three mutations of the TIGR (Trabecular meshwork-Induced Glucocorticoid Response) gene were shown to be responsible for the disease in several American families and in unrelated POAG patients. We now describe five new mutations in eight French families. All mutations known to date appear to concentrate in the evolutionarily conserved C-terminal domain of TIGR which bears homology to frog olfactomedin, an extracellular matrix glycoprotein of the olfactory epithelium, to rat and human neuronal olfactomedin-related proteins and to F11C3.2, a protein from Caenorhabditis elegans . Moreover, this conserved domain of TIGR is encoded by a single exon to which mutation screening could be limited. Surprisingly, the TIGR message, which is abundantly transcribed in the trabecular meshwork and also in the ciliary body and the sclera, is not expressed in the optic nerve whose degeneration is, however, the primary lesion of POAG.
authors.affiliation: INSERM U25, Hôpital Necker, 161 rue de Sèvres, 75743 Paris cedex 15, France.
authors.forename: M F
authors.initials: MF
authors.lastname: Adam
authors.forename: A
authors.initials: A
authors.lastname: Belmouden
authors.forename: P
authors.initials: P
authors.lastname: Binisti
authors.forename: A P
authors.initials: AP
authors.lastname: Brézin
authors.forename: F
authors.initials: F
authors.lastname: Valtot
authors.forename: A
authors.initials: A
authors.lastname: Béchetoille
authors.forename: J C
authors.initials: JC
authors.lastname: Dascotte
authors.forename: B
authors.initials: B
authors.lastname: Copin
authors.forename: L
authors.initials: L
authors.lastname: Gomez
authors.forename: A
authors.initials: A
authors.lastname: Chaventré
authors.forename: J F
authors.initials: JF
authors.lastname: Bach
authors.forename: H J
authors.initials: HJ
authors.lastname: Garchon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002648:Child; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins; D019143:Evolution, Molecular; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D015894:Genome, Human; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009831:Olfactory Mucosa; D009928:Organ Specificity / Q000235:genetics; D017354:Point Mutation; D011892:Rana catesbeiana; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014129:Trabecular Meshwork; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin; C081451:olfactomedin