Confirmation of the Adult-Onset Primary Open Angle Glaucoma Locus GLC1B at 2cen-q13 in an Australian Family

Abstract

Primary open-angle glaucoma (POAG) is genetically heterogeneous, with 6 named POAG loci GLC1A-F mapped and genes myocilin (MYOC) and optineurin (OPTN) identified at 2 of the loci. Using penetrance-model-free methods, we screened the POAG loci GLC1A-F in an extended Australian pedigree, using 3–5 markers within each locus. p values of less than 0.05 were obtained empirically using SimWalk2 and exactly using Genehunter for 2 markers within the GLC1B region on chromosome 2. Fine mapping of this region produced pvalues of 0.01 or less at 5 markers flanked by D2S1897 and D2S2269. The 9 cM haplotype of interest overlaps the original GLC1B region. These results provide supportive evidence for the GLC1B locus on chromosome 2cen-q13 and verify the existence of POAG susceptibility gene in this region, increasing the likelihood of gene identification.

Major review: Molecular genetics of primary open-angle glaucoma

“…Clinically, mutations in OPTN lead to NTG. This contrasts sharply with patients who have MYOC - associated POAG, which is consistently hypertensive (Ariani et al, 2006; Charlesworth et al, 2006; Hauser et al, 2006b; Rezaie et al, 2002). Among all OPTN mutations, E50K has been most clearly shown to cause glaucoma (Aung et al, 2005).…”

Identification of Novel Genetic Loci for Intraocular Pressure

“…Recently, a study of a single 4-generation, Tasmanian family with glaucoma, which included 15 living descendants, identified a 9-cM region on chromosome 2 (exact nonparametric link-age=0.005) that overlaps with GLC1B, confirming this as a glaucoma locus. 30 Our findings suggest that this region on chromosome 2 may harbor a single gene that influences systemic blood pressure, with strong effects on glaucoma, or possibly 2 or more genes in close proximity that influence pressure and glaucoma independently.…”