title: Identification of a new 'TIGR' mutation in a family with juvenile-onset primary open angle glaucoma.
abstract: Positional mapping of families segregating for juvenile-onset primary open angle glaucoma (JOAG) has previously identified a locus (GLCIA) for this condition on the long arm of chromosome I. Recently, three mutations in the TIGR gene (Trabecular meshwork Inducible Gluco-corticoid Response protein) have been described in a total of ten familial, three sporadic, and one normal subject. One of the familial cases has also been indicated to be of an adult-onset type. Herein, we report the identification of a new mutation in the TIGR gene in a six generation well-documented Edinburgh family with JOAG. We have sampled and screened the living affected members of this family and identified an 'A'-to-'G' transition at amino acid 337 that has changed the glutamine (Gln) to arginine (Arg). This newly identified mutation resides 27 amino acids 5-prime from the previously reported mutation of Gly-to-Val. This mutation created a new MspI restriction site that has co-segregated perfectly with inherited affected haplotype of the pedigree and, furthermore, it has not been observed in 142 chromosomes of randomly selected subjects of the same population. This report, therefore, confirms the role of the TIGR gene in the etiology of JOAG and adds a new mutation to the three reported previously.
authors.affiliation: Department of Surgery, University of Connecticut Health Center, Farmington 06030-1110, USA.
authors.forename: D
authors.initials: D
authors.lastname: Stoilova
authors.forename: A
authors.initials: A
authors.lastname: Child
authors.forename: G
authors.initials: G
authors.lastname: Brice
authors.forename: R P
authors.initials: RP
authors.lastname: Crick
authors.forename: B W
authors.initials: BW
authors.lastname: Fleck
authors.forename: M
authors.initials: M
authors.lastname: Sarfarazi
mesh_terms: D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006023:Glycoproteins; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D014129:Trabecular Meshwork; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D005819:Genetic Markers; D006023:Glycoproteins; D000099179:Myocilin