GLC1F, a new primary open-angle glaucoma locus, maps to 7q35-q36

Background: A large family with adult-onset primary open-angle glaucoma (PO AG) was identified. Objective: To initiate a genome-wide scan to map the POAG locus in this fam ily. Methods: Blood samples or buccal swabs were obtained from 25 members of a l arge family with POAG after informed consent was obtained. Members and thei r spouses were evaluated clinically for POAG on the basis of intraocular pr essures, cupping of discs, and visual fields. DNA samples were used for a g enome-wide screen using microsatellite markers. Results: Ten affected family members in 4 generations showed evidence of PO AG including intraocular pressures of 22 mm Hg or more, and/or optic cup-di sc ratios of 0.6 or more, and/or visual field defects consistent with glauc omatous damage. Primary open-angle glaucoma segregated as an autosomal domi nant trait, with the disease locus mapping to 7q35-q36 between markers D7S2 442 and D7S483 with a multipoint lod score of 4.06. Conclusion: A sixth gene for POAG (GLC1F) has been mapped to 7q35-q36 in a family with at least 4 generations affected. Clinical Relevance: The mapping of this locus further confirms that primary open-angle glaucoma is a heterogeneous group of diseases with at least 6 d ifferent loci resulting in a similar phenotype. The eventual ability to cla ssify which major POAG gene an affected person carries could have ramificat ions for selecting the most effective treatment regimen for that person.