Purpose: Two genes for adult-onset primary open-angle glaucoma have been mapped to chromosomes 2cen-q13 and 3q21-q24. We studied a family with adult-onset primary open-angle glaucoma in which the disease did not map to these two chromosomal regions.
Methods: We ascertained a four-generation family with adult-onset primary open-angle glaucoma in which the disease status of individuals was objectively assigned using defined criteria. Complete ophthalmologic examinations, visual field testing, optic nerve head photographs, and venous blood samples were obtained. Family members were genotyped using polymerase chain reaction amplification of microsatellite polymorphic markers. Linkage analysis was performed and lod scores were calculated. Haplotype transmission data were analyzed.
Results: A total of 20 subjects in three successive generations agreed to participate in the study. This included samples from eight affected subjects, one glaucoma suspect, one normal individual, and two spouses in generations II and III, and an additional eight individuals in generation IV. The phenotype in this family appears to be variable, with onset of visual field loss in middle age, followed by modest elevation of intraocular pressure and progression of the disease in older individuals. Linkage was established with a group of DNA markers located in the 8q23 region. A lod score value of 3.61 was obtained using marker D8S1471. Three other markers from the same region gave lod score values of over 3.0. Haplotype transmission data identified two recombination events that placed the gene in a 6.3-cM region flanked by D8S1830 and D8S592. The disease-bearing haplotype was inherited by eight affected subjects and three glaucoma suspects.
Conclusion: We present evidence for a third adult-onset primary open-angle glaucoma locus (GLC1D) on chromosome 8q23. The genetic heterogeneity of adult-onset glaucoma is evident from the multiplicity of chromosomal loci associated with this disease.