Genetic heterogeneity in Hispanic families with autosomal dominant, juvenile-onset, primary open angle glaucoma

Purpose: A gene for autosomal dominant, juvenile-onset, primary open angle glaucoma has been previously mapped to the 1q21-31 region. We studied two Hispanic families with this disease to determine if their disease genes also map to this region. Methods: Individuals were considered as being affected if they had IOP > 30 mm Hg (without treatment) and glaucomatous optic nerve damage or visual field defects. Persons older than 40 years with intraocular pressure below 22 and no evidence of optic nerve damage or visual field loss were scored as unaffected. Individuals not falling into these two categories were considered unknown. Genomic DNA was extracted from blood samples and subjected to PCR-based microsatellite marker analysis. Computer-based linkage analysis was used to determine if the disease gene mapped to chromosome 1q21-31. Results: In Family 1, the disease gene was linked to the chromosome 1q21-31 region previously identified by other researchers. Markers D1S212 and D1S218 produced lod scores of 3.00 and 2.96, respectively. In Family 2, the disease gene was excluded from this region. Markers D1S212 and D1S218 produced lod scores of -6.48 and -6.35 respectively with similar results for nearby markers. Haplotype analysis also excluded the disease gene in Family 2 from chromosome 1q21-31. Conclusions: Our Hispanic families showed genetic heterogeneity with respect to autosomal dominant, juvenile-onset, primary open angle glaucoma.