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M Maselli, S Lynch, G Yanagi, JR Shi, EL DelBono, JL Haines, JL Wiggs; Genomic Screen for Genes Responsible for Early Onset Open Angle Glaucoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3396.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:One gene responsible for early onset primary open angle glaucoma has been cloned (TIGR/Myocilin). However, previous studies have shown that only 8-20% of families affected by dominant juvenile glaucoma have mutations in this gene. Using a collection of autosomal dominant juvenile glaucoma families without mutations in the TIGR/Myocilin gene, we have performed a genome-wide screen to identify the chromosomal locations of additional genes responsible for this condition. Methods:Twenty-five pedigrees consisting of a minimum of three affected individuals in two generations (198 total individuals, 105 affected) were used for this study. Juvenile glaucoma was defined as: age of diagnosis before age 35, IOP greater than 22 in both eyes, glaucomatous optic nerve damage in both eyes, and visual field loss in at least one eye. Individuals with secondary causes of glaucoma, including evidence of anterior segment dysgenesis and pigment dispersion syndrome, were excluded. For the initial genome screen, only affected pedigree members and spouses were included in the analysis. Results:Two hundred thirty eight markers spanning the human genome at approximately 10 cM intervals were analyzed. Two-point lod scores were calculated using an autosomal dominant model. Five regions on chromosomes 3, 5, 9, 12 and 20 demonstrated initially interesting results (two point lod score ≷1.0). Multipoint analyses of chromosomes 5, 9 and 20 resulted in a higher lod scores for markers located in these regions, with a peak score of 3.3 on chromosome 9. Haplotype analysis identified a 20 cM candidate interval on chromosome 9. Conclusion:Results from the initial genome screen identified five regions that demonstrated interesting results. Follow-up studies have identified a 20 cM region on chromosome 9 that consistently segregates with the disease phenotype in the majority of affected families. Analysis of candidate genes located in this region is currently under way.
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