Fernandez-Martinez, Lorena and Letteboer, Stef and Mardin, Christian Y. and Weisschuh, Nicole and Gramer, Eugen and Weber, Bernhard H. F. and Rautenstrauss, Bernd and Ferreira, Paulo A. and Kruse, Friedrich E. and Reis, Andre and Roepman, Ronald and Pasutto, Francesca (2011) Evidence for RPGRIP1 gene as risk factor for primary open angle glaucoma. EUROPEAN JOURNAL OF HUMAN GENETICS, 19 (4). pp. 445-451. ISSN 1018-4813, 1476-5438
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Glaucoma is a genetically heterogeneous disorder and is the second cause of blindness worldwide owing to the progressive degeneration of retinal ganglion neurons. Very few genes causing glaucoma were identified to this date. In this study, we screened 10 candidate genes of glaucoma between the D14S261 and D14S121 markers of chromosome 14q11, a critical region previously linked to primary open-angle glaucoma (POAG). Mutation analyses of two large cohorts of patients with POAG, normal tension glaucoma (NTG) and juvenile open-angle glaucoma (JOAG), and control subjects, found only association of non-synonymous heterozygous variants of the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) with POAG, NTG and JOAG. The 20 non-synonymous variants identified in RPGRIP1 were all distinct from variants causing photoreceptor dystrophies and were found throughout all but one domain (RPGR-interacting domain) of RPGRIP1. Among them, 14 missense variants clustered within or around the C2 domains of RPGRIP1. Yeast two-hybrid analyses of a subset of the missense mutations within the C2 domains of RPGRIP1 shows that five of them (p.R598Q, p.A635G, p.T806I, p.A837G and p.I838V) decrease the association of the C2 domains with nephrocystin-4 (NPHPH). When considering only these five confirmed C2-domain mutations, the association remains statistically significant (P=0.001). Altogether, the data support that heterozygous non-synonymous variants of RPGRIP1 may cause or increase the susceptibility to various forms of glaucoma and that among other factors, physical impairment of the interaction of RPGRIP1 with different proteins may contribute to the pathogenesis of forms of glaucoma. European Journal of Human Genetics (2011) 19, 445-451; doi:10.1038/ejhg.2010.217; published online 12 January 2011
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LEBER CONGENITAL AMAUROSIS; GENOME-WIDE SCAN; SUBCELLULAR-LOCALIZATION; RETINITIS-PIGMENTOSA; GERMAN PATIENTS; OPTIC DISC; MUTATIONS; IDENTIFICATION; VARIANTS; EXPRESSION; glaucoma; RPGRIP1; mutation screening |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Jun 2020 08:17 |
| Last Modified: | 23 Jun 2020 08:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21070 |
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