title: Novel mutations in the TIGR gene in early and late onset open angle glaucoma.
abstract: A gene for juvenile onset, open angle glaucoma (JOAG) has been localized to chromosome 1q21-31 in several families. Mutations in the trabecular meshwork-induced glucocorticoid response protein (TIGR) gene, which maps to this region, recently have been found in families segregating both JOAG and a later onset form of primary open angle glaucoma (POAG). We have analysed the TIGR gene in two families; one Spanish family segregating autosomal dominant JOAG and an Irish family with a later onset form of autosomal dominant POAG. We have found a G-T transversion in the first base of codon 426 in all affected members of the Spanish family, which results in a valine to phenylalanine amino acid substitution. We have also found a G-A transition at the first base of codon 367 that segregates through all but one branch of the Irish family and results in a glycine to arginine amino acid substitution. Members of this family that carry the Gly367Arg change also share a common haplotype that is neither present in any of the unaffected members of the family, nor in the branch that does not segregate the mutation. Identification of further mutations in the TIGR gene increases its importance in the etiology of open angle glaucoma.
authors.affiliation: Department of Genetics, Trinity College, Dublin, Ireland. fmnsergh@biotech.bio.tcd.ie
authors.forename: F C
authors.initials: FC
authors.lastname: Mansergh
authors.forename: P F
authors.initials: PF
authors.lastname: Kenna
authors.forename: C
authors.initials: C
authors.lastname: Ayuso
authors.forename: A S
authors.initials: AS
authors.lastname: Kiang
authors.forename: P
authors.initials: P
authors.lastname: Humphries
authors.forename: G J
authors.initials: GJ
authors.lastname: Farrar
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D008040:Genetic Linkage; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007494:Ireland; D008297:Male; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D013030:Spain; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin