A new locus (GLC1H) for adult-onset primary open-angle glaucoma maps to the 2p15-p16 region.

Objective To map new genetic loci for adult-onset primary open-angle glaucoma (POAG) by using families previously unlinked to GLC1A - GLC1F . Methods Initial genome scan and subsequent saturation mapping confirmed linkage to a locus on chromosome 2p15-p16. Forty-nine DNA samples from a single family with POAG with 113 individuals were used in this study. The 10 affected members of this family had an average age at onset of 64 years, moderate to high intraocular pressure, glaucomatous visual field loss, and cup-disc ratios of 0.6 to 0.9. Results Haplotype construction in 9 available affected subjects established a single inherited chromosome from D2S123 to D2S2165 , within an 11-megabase (Mb) region. Further analysis revealed no recombination with 8 consecutive DNA markers ( D2S1364-D2S2332 ) and provided a maximum logarithm of the odds (LOD) score of 2.97 for D2S370 . Six additional families also showed consistent linkage and 1 affected recombination may further confine this locus to an 8.3-Mb region ( D2S2352 - D2S2165 ). Combined analysis of 7 families provided a maximum LOD score of 9.30 with D2S2320 . Conclusions A new genetic locus ( GLC1H ) for adult-onset POAG maps to the 2p15-p16 region. Clinical Relevance Mapping of the GLC1H locus and eventual identification of its defective gene will help to develop diagnostic tools and effective treatments for this condition.