CLINICAL-MOLECULARGENETIC CORRELATIONS IN GLAUCOMAS
C.Y. Mardin1 , I. Velten1 , K. Michels-Rautenstrauss2 , B. Rautenstrauss2
Aim of this study was to investigate the clinical-moleculargenetic correlation in patients with primary open-angle glaucoma concerning mutations of the TIGR (trabecular meshwork inducible glucocorticoid response protein) gene locus, described by Stone et al 1997 (Science).
Patients and methods: 225 patients (glaucoma suspects and primary open- angle glaucoma) were examined by gonioscopy, morphometry of the optic disc, perimetry and by a 24h-intraocular pressure profile. For the analysis of the genotype genomic DNA was extracted and amplified from 15 ml EDTA-blood. Mutation analysis of the TIGR-gene was done by SSCP- analysis and sequencing. As controls served normal individuals and non related family members.
Results: In two families with autosomal dominantly inherited juvenile open-angle glaucoma (GLC1A), in 6,4 % of the ocular hypertensives, in 4% of the patients with positive family history for glaucoma and in 6% of the sporadic cases of open angle glaucoma a mutation in the third exon of the TIGR- gene was detected. One patient with a Gln368Stop-mutation showed the phenotype of a normal pressure glaucoma. None of the normal controls showed a TIGR-mutation.
Conclusions: Mutations of the TIGR-gene were also found in sporadic cases of open-angle glaucoma. Mutations of the TIGR- gene need not lead to glaucoma with high intraocular pressures. Further studies might show the relevance and meaning of TIGR-mutations with respect to the already obvious phenotypic variability.
Supported by Deutsche Forschungsgemeinschaft (SFB 589)
1Augenklinlk mit Poliklinik, Universität Erlangen-Nürnberg, Schwabachanlage 8, 91054 Erlangen. 2 Institut für Humangenetlk, Universität Erlangen-Nümberg, Schwabachanlage 10, 91054 Erlangen.