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C. Pang, B.J. Fan, O. Canlas, D.Y. Wang, P.O. S. Tam, D.S. C. Lam, D.S. P. Fan, C.Y. Lam, V. Raymond, R. Ritch; A Novel Locus for Juvenile–Onset Primary Open–Angle Glaucoma Maps at Chromosome 5q . Invest. Ophthalmol. Vis. Sci. 2005;46(13):42.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Six genetic loci have been reported as contributing to primary open–angle glaucoma susceptibility by genetic linkage analysis, and 2 causative genes have been identified (MYOC & OPTN). This study was designed to map the disease–associated locus of a large Philippine family with autosomal dominant juvenile–onset primary open angle glaucoma (JOAG). Methods: MYOC and OPTN were screened for mutations by sequencing. Genome–wide scan was performed on 27 participants of the JOAG family by using the ABI MD–10 marker set with an average spacing of 10cM and utilizing the Genescan and Genotyper packages to call genotypes. Prior to linkage analysis, all Mendelian inconsistencies in the pedigree data were eliminated. Two–point analyses were performed on the genome scan results with the MLINK under an autosomal dominant inheritance model. For fine mapping, additional markers flanking the most promising regions were analyzed in a similar fashion. Regions containing markers with LOD score values > 3.0 were further analyzed by multipoint analyses using the LINKMAP program. The significance of LOD scores was tested with simulation analyses using FASTLINK. Haplotypes were constructed using Simwalk2. Results: None of the family members carried a MYOC or OPTN mutation. Genome–wide scan suggested linkage with DNA markers to the 5q23–q33 region, which was confirmed by fine mapping with additional markers. A maximum LOD score value of 4.82 at θ = 0.00 was obtained for marker D5S2011. Markers D5S2098, D5S471 and D5S2497 had LOD score values of 4.71, 4.24 and 3.35 at θ = 0.00 respectively. Five other markers within the region had LOD scores over 2.0. Haplotype analysis and recombination mapping further confined this region to 5q22.2–q32 within a genetic distance of ∼ 30.84 cM flanked by D5S2027 and D5S2090. Conclusions: A novel genetic locus on 5q22.2–q32 has been identified for JOAG. Our results provide new evidence that JOAG is genetically heterogeneous and are an important step towards the identification of a novel gene for this severe eye disorder.
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