{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:19:39Z","timestamp":1768911579874,"version":"3.49.0"},"reference-count":19,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1998,12]]},"abstract":"<jats:p>Mutations in the trabecular meshwork induced glucocorticoid response protein (TIGR) or myocilin (MYOC) has recently been shown to cause juvenile onset primary open angle glaucoma (JOAG). In this study, we identified two new mutations (Asp380Ala and Ser502Pro) in two British families and another (Pro370Leu) in a French-Canadian family. These mutations were not present in a total of 106 normal chromosomes. In another Turkish family with JOAG, we also detected a sequence variant that was proven to be an amino acid polymorphism (Arg76Lys). No other sequence changes were found in the entire coding region and splice junctions of the TIGR\/MYOC gene in this family. However, it is still possible that mutations either in the TIGR promoter or in another neighbouring gene could cause glaucoma in this JOAG family. Our results confirm the role of the TIGR\/MYOC gene in the aetiology of the JOAG phenotype.<\/jats:p>","DOI":"10.1136\/jmg.35.12.989","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"989-992","source":"Crossref","is-referenced-by-count":43,"title":["Novel TIGR\/MYOC mutations in families with juvenile onset primary open angle glaucoma."],"prefix":"10.1136","volume":"35","author":[{"given":"D","family":"Stoilova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Child","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"Brice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Desai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Barsoum-Homsy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Ozdemir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Chevrette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M F","family":"Adam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H J","family":"Garchon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Pitts Crick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Sarfarazi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1998,12,1]]},"reference":[{"key":"ref_1","first-page":"71725","article-title":"Classification of the glaucomas","volume":"2","author":"Shields, M.B.; Ritch, R.; Krupin, T.","year":"1996","unstructured":"Shields MB, Ritch R, Krupin T. Classification of the glaucomas. In: Ritch R, Shields MB, Krupin T, eds. The glaucomas. St. Louis: Mosby-Year Book Inc, 1996;2:71725."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1136\/bjo.80.5.389","article-title":"Number of people with glaucoma worldwide","volume":"80","author":"Quigley, H.A.","year":"1996","unstructured":"Quigley HA. Number of people with glaucoma worldwide. Br] Ophthalniol 1996;80:389-93.","journal-title":"Br] Ophthalniol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1016\/S0002-9394(48)91298-7","article-title":"The etiology, symptomatology and treatment of juvenile glaucoma","volume":"31","author":"Ellis, O.H.","year":"1948","unstructured":"Ellis OH. The etiology, symptomatology and treatment of juvenile glaucoma. Am _Ophthalmol 1948;31:1589-96.","journal-title":"Am _Ophthalmol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S0161-6420(13)31615-7","article-title":"Clinical features and linkage analysis of a family with autosomal dominant juvenile glaucoma","volume":"100","author":"Johnson, A.T.; Drack, A.V.; Kwitek, A.E.; Cannon, R.L.; Stone, E.M.; Alward, W.L.","year":"1993","unstructured":"Johnson AT, Drack AV, Kwitek AE, Cannon RL, Stone EM, Alward WL. Clinical features and linkage analysis of a family with autosomal dominant juvenile glaucoma. Ophthalmology 1993;100:524-9.","journal-title":"Ophthalmology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/S0002-9394(14)70314-9","article-title":"Genetic clues to glaucoma's secrets. The Jackson memorial lecture. Part 2","volume":"117","author":"Lichter, PR","year":"1994","unstructured":"Lichter PR. Genetic clues to glaucoma's secrets. The Jackson memorial lecture. Part 2. Am J Ophthalmol 1994;117:706-27.","journal-title":"Am J Ophthalmol"},{"key":"ref_6","first-page":"47","article-title":"Genetic linkage of familial open angle glaucoma to chromosome 1q21 -q3 1","volume-title":"Nat Genet","volume":"4","author":"Sheffield, V.C.; Stone, E.M.; Alward, W.L.","year":"1993","unstructured":"Sheffield VC, Stone EM, Alward WL, et al. Genetic linkage of familial open angle glaucoma to chromosome 1q21 -q3 1. Nat Genet 1993;4:47-50."},{"key":"ref_7","first-page":"272","article-title":"Molecular genetics of glaucoma: mapping of the first five \"GLC\" loci","volume":"60","author":"Raymond, V.","year":"1997","unstructured":"Raymond V. Molecular genetics of glaucoma: mapping of the first five \"GLC\" loci. AmJ Hum Genet 1997;60:272-7.","journal-title":"AmJ Hum Genet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1093\/hmg\/6.10.1667","article-title":"Recent advances in molecular genetics of glaucomas","volume":"6","author":"Sarfarazi, M.","year":"1997","unstructured":"Sarfarazi M. Recent advances in molecular genetics of glaucomas. Hum Mol Genet 1997;6:1667-77.","journal-title":"Hum Mol Genet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1126\/science.275.5300.668","article-title":"Identification of a gene that causes primary open angle glaucoma","volume":"275","author":"Stone, E.M.; Fingert, J.H.; Alward, W.L.M.","year":"1997","unstructured":"Stone EM, Fingert JH, Alward WLM, et al. Identification of a gene that causes primary open angle glaucoma. Science 1997;275:668-70.","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1159\/000310780","article-title":"Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product","volume":"211","author":"Polansky, J.; Fauss, D.; Chen, P.","year":"1997","unstructured":"Polansky J, Fauss D, Chen P, et al. Cellular pharmacology and molecular biology of the trabecular meshwork inducible glucocorticoid response gene product. Ophthalniologica 1997;211:126-39.","journal-title":"Ophthalniologica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1006\/geno.1997.4682","article-title":"A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: molecular cloning, tissue expression, and chromosomal mapping","volume":"41","author":"Kubota, R.; Noda, S.; Wang, Y.","year":"1997","unstructured":"Kubota R, Noda S, Wang Y, et al. A novel myosin-like protein (myocilin) expressed in the connecting cilium of the photoreceptor: molecular cloning, tissue expression, and chromosomal mapping. Genomics 1997;41:360-9.","journal-title":"Genomics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1093\/hmg\/6.12.2091","article-title":"Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma","volume":"6","author":"Adam, M.F.; Belmouden, A.; Binisti, P.","year":"1997","unstructured":"Adam MF, Belmouden A, Binisti P, et al. Recurrent mutations in a single exon encoding the evolutionarily conserved olfactomedin-homology domain of TIGR in familial open-angle glaucoma. Hum Mol Genet 1997;6:2091-7.","journal-title":"Hum Mol Genet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0014-5793(97)00934-4","article-title":"Cloning and characterization of substracted cDNA from human ciliary body including TIGR, a protein involved in juvenile open angle glaucoma and homologous to olfactomedin","volume":"413","author":"Ortego, J.; Escribano, J.; Coca-Prados, M.","year":"1997","unstructured":"Ortego J, Escribano J, Coca-Prados M. Cloning and characterization of substracted cDNA from human ciliary body including TIGR, a protein involved in juvenile open angle glaucoma and homologous to olfactomedin. FEBS Lett 1997;413:349-53.","journal-title":"FEBS Lett"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3109\/13816819709057124","article-title":"Identification of a new 'TIGR' mutation in a family with juvenile-onset primary open angle glaucoma","volume":"18","author":"Stoilova, D.; Child, A.; Brice, G.; Crick, R.P.; Fleck, B.W.; Sarfarazi, M.","year":"1997","unstructured":"Stoilova D, Child A, Brice G, Crick RP, Fleck BW, Sarfarazi M. Identification of a new 'TIGR' mutation in a family with juvenile-onset primary open angle glaucoma. Ophthal Genet 1997;18:109-18.","journal-title":"Ophthal Genet"},{"key":"ref_15","first-page":"273","article-title":"Retinal circulation in primary open-angle glaucoma tested by videodensitometric image analysis","volume":"24","author":"Suzuki, R.; Sugihara, I.; Kurimoto, S.","year":"1992","unstructured":"Suzuki R, Sugihara I, Kurimoto S. Retinal circulation in primary open-angle glaucoma tested by videodensitometric image analysis. Ann Ophthalmol 1992;24:273-7.","journal-title":"Ann Ophthalmol"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s004390050661","article-title":"Juvenile open angle glaucoma: fine mapping of the TIGR gene to lq24.3-q25.2 and mutation analysis","volume":"102","author":"Michels-Rautenstraus, K.G.; Mardin, C.Y.; Budde, W.M.","year":"1998","unstructured":"Michels-Rautenstraus KG, Mardin CY, Budde WM, et al. Juvenile open angle glaucoma: fine mapping of the TIGR gene to lq24.3-q25.2 and mutation analysis. Hum Genet 1998;102: 103-6.","journal-title":"Hum Genet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1006\/geno.1996.4491","article-title":"Recombinational and physical mapping of the locus for primary open-angle glaucoma (GLC1A) on chromosome lq23-q25","volume":"39","author":"Belmouden, A.; Adam, M.F.; Dupont de Dinechi, J.","year":"1997","unstructured":"Belmouden A, Adam MF, Dupont de Dinechi J, et al. Recombinational and physical mapping of the locus for primary open-angle glaucoma (GLC1A) on chromosome lq23-q25. Genomics 1997;39:348-58.","journal-title":"Genomics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1093\/hmg\/6.4.641","article-title":"Identification of three different truncating mutations in cytochrome P4501 B 1 (CYPlBl) as the principal cause of primary congenital glaucoma (buphthalmos) in families linked to the GLC3A locus on chromosome 2p21","volume":"6","author":"Stoilov, I.; Akarsu, A.N.; Sarfarazi, M.","year":"1997","unstructured":"Stoilov I, Akarsu AN, Sarfarazi M. Identification of three different truncating mutations in cytochrome P4501 B 1 (CYPlBl) as the principal cause of primary congenital glaucoma (buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Hum Mol Genet 1997;6:641-7.","journal-title":"Hum Mol Genet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1086\/301764","article-title":"Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p2l results from mutations disrupting either the hinge region or the conserved core structure of cytochrome P450B 1","volume":"62","author":"Stoilov, I.; Akarsu, A.; Alozie, I.","year":"1998","unstructured":"Stoilov I, Akarsu A, Alozie I, et al. Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p2l results from mutations disrupting either the hinge region or the conserved core structure of cytochrome P450B 1. Am J Hum Genet 1998;62:573-84.","journal-title":"Am J Hum Genet"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.35.12.989","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T03:44:12Z","timestamp":1759722252000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.35.12.989"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,12]]},"references-count":19,"journal-issue":{"issue":"12","published-online":{"date-parts":[[1998,12,1]]},"published-print":{"date-parts":[[1998,12]]}},"alternative-id":["10.1136\/jmg.35.12.989"],"URL":"https:\/\/doi.org\/10.1136\/jmg.35.12.989","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,12]]}}}