Purpose:  Primary open angle glaucoma (POAG) is a complex heterogeneous disease. The aim of this study was to describe the POAG phenotype in individuals who harbour the novel GLC1L disease‐associated haplotype in a large pedigree where the Myocilin Gln368STOP mutation also segregates.

Methods:  The clinical findings from 24 subjects with POAG from the GTAS02 family recruited as part of the Glaucoma Inheritance Study of Tasmania (GIST) were compared relative to genotype status. The previously identified GLC1L disease haplotype encompasses a chromosomal region of 8.3 centimorgans bounded by the markers D3S3521 and D3S1289 on 3p21‐22.

Results:  In subjects with the GLC1L disease haplotype (with or without Gln368STOP), the POAG phenotype was characterized by a mean age at diagnosis of 54.3 years, and mean maximum recorded intraocular pressure (IOP) of 23.9 mmHg. The mean maximum recorded IOP was lower in subjects with the predicted disease haplotype and no Gln368STOP mutation, compared with subjects with the predicted disease haplotype and presence of the Gln368STOP mutation (P = 0.02). Presence of the Gln368STOP mutation was significantly more common in those with the predicted disease haplotype than those without (P = 0.04). In the four subjects carrying the GLC1L disease‐associated haplotype without the Gln368STOP mutation, a normotensive glaucoma (mean maximum recorded IOP 15 mmHg, range 13–17 mmHg) was present.

Conclusions:  The GLC1L locus may be associated with glaucoma in the absence of elevated IOP. Discovery of the specific gene within the GLC1L locus on 3p21‐22 would provide a useful addition to our ability to offer genetic testing and counselling to POAG individuals and their families.