Juvenile open angle glaucoma: fine mapping of the TIGR gene to 1q24.3-q25.2 and mutation analysis

Abstract

Autosomal dominant juvenile open angle glaucoma (JOAG) is an early-onset form of primary open angle glaucoma (POAG), which has been linked to chromosome 1q21-q31. Recently, mutations in the trabecular meshwork inducible glucocorticoid response gene (TIGR), one of the candidate genes mapped in this region, were identified in glaucoma patients of several families. We screened for mutations of the TIGR gene in two German families with JOAG and in 100 unselected sporadic cases of POAG. In the first family we identified a Pro370Leu mutation and in the second family a Gly367Arg mutation cosegregating with the glaucoma phenotype. No pathogenic mutation was found in 100 sporadic cases but a Tyr347Tyr polymorphism was found in two patients. Furthermore, fluorescence in situ hybridization (FISH) analysis was used to map a TIGR-specific yeast artificial chromosome to 1q24.3-q25.2.

Myocilin Expression in the Astrocytes of the Optic Nerve Head

“…Since the first finding of mutations in the MYOC/ TIGR gene in the patients with juvenile onset POAG (11), more mutations were found in the same juvenile onset POAG patients throughout the world (15)(16)(17)(18)(19)(20)(21)(22)(23). Mutations in the MYOC/TIGR gene were also found even in the late onset POAG patients (17-19, 21, 24).…”

Regulation of human myocilin/TIGR gene transcription in trabecular meshwork cells and astrocytes: role of upstream stimulatory factor

“…Stone et al (Stone et al 1997) identi®ed three mutations in the gene for MYOC/TIGR, which lies within the interval on chromosome 1 that was originally associated with juvenile open angle-glaucoma (GLC1A) (Shef®eld et al 1993;Richards et al 1994;Wiggs et al 1994). Subsequently, mutations in the same gene of patients with GLC1A-linked juvenile open-angle glaucoma were also reported by other researchers (Adam et al 1997;Kee & Ahn 1997;Stoilova et al 1997;Suzuki et al 1997;Brezin et al 1998;Mansergh et al 1998;Michels-Rautenstrauss et al 1998). Juvenile open-angle glaucoma refers to a subset of POAG that has an earlier age of onset, a highly penetrant mode of inheritance and is usually associated with a high IOP requiring early surgical treatment (Wiggs et al 1995;Johnson et al 1996).…”

Myocilin mutations in a population-based sample of cases with open-angle glaucoma: the Rotterdam Study

“…It is now generally accepted that POAG is a complex disease, which is a result of multiple and interactive genetic and environmental effects. Although six chromosomal loci [26,27,30,35,38,39] and five possibly involved genomic regions [37] for POAG have been described [25], the only causative gene known at present is myocilin (MYOC) [19,32], which codes for the MYOC protein [21,22].…”