Background: A large family with adult-onset primary open-angle glaucoma (POAG) was identified.
Objective: To initiate a genome-wide scan to map the POAG locus in this family.
Methods: Blood samples or buccal swabs were obtained from 25 members of a large family with POAG after informed consent was obtained. Members and their spouses were evaluated clinically for POAG on the basis of intraocular pressures, cupping of discs, and visual fields. DNA samples were used for a genome-wide screen using microsatellite markers.
Results: Ten affected family members in 4 generations showed evidence of POAG including intraocular pressures of 22 mm Hg or more, and/or optic cup-disc ratios of 0.6 or more, and/or visual field defects consistent with glaucomatous damage. Primary open-angle glaucoma segregated as an autosomal dominant trait, with the disease locus mapping to 7q35-q36 between markers D7S2442 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 different loci resulting in a similar phenotype. The eventual ability to classify which major POAG gene an affected person carries could have ramifications for selecting the most effective treatment regimen for that person.