Evidence for RPGRIP1 gene as risk factor for primary open angle glaucoma

Journal article

Publication Details

Author(s): Fernández Martinez L, Letteboer S, Mardin CY, Weisschuh N, Gramer E, Weber BHF, Rautenstrauß B, Ferreira PA, Kruse F, Reis A, Roepman R, Pasutto F
Journal: European journal of human genetics
Publication year: 2011
Volume: 19
Journal issue: 4
Pages range: 445-51
ISSN: 1018-4813


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 RPGRIP1with different proteins may contribute to the pathogenesis of forms of glaucoma.

FAU Authors / FAU Editors

Kruse, Friedrich Prof. Dr.
Lehrstuhl für Augenheilkunde

External institutions with authors

Duke University
Radboud University Nijmegen
Universität Regensburg
Universitätsklinikum Tübingen
Universitätsklinikum Würzburg

How to cite

Fernández Martinez, L., Letteboer, S., Mardin, C.Y., Weisschuh, N., Gramer, E., Weber, B.H.F.,... Pasutto, F. (2011). Evidence for RPGRIP1 gene as risk factor for primary open angle glaucoma. European journal of human genetics, 19(4), 445-51. https://dx.doi.org/10.1038/ejhg.2010.217

Fernández Martinez, Lorena, et al. "Evidence for RPGRIP1 gene as risk factor for primary open angle glaucoma." European journal of human genetics 19.4 (2011): 445-51.


Last updated on 2018-06-10 at 02:53