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IR Stoilov, M Sarfarazi; The Third Genetic Locus (GLC3C) for Primary Congenital Glaucoma (PCG) Maps to Chromosome 14q24.3 . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3015.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To identify the genetic locus associated with primary congenital glaucoma phenotype in a multigeneration consanguineous family unlinked to both GLC3A and GLC3B loci. Methods: A five-generation consanguineous family segregating for primary congenital glaucoma in an autosomal-recessive manner was ascertained and DNA samples were obtained from 13 individuals (4 affected). Family members were genotyped with set of polymorphic DNA markers spanning the PCG loci, haplotypes constructed and transmission data evaluated. Automated fluorescent genotyping was performed with CHLC/Weber human screening set version 9/9a (Research Genetics). Results: Critical recombination events revealed by haplotype analysis with genetic markers spanning loci GLC3A and GLC3B indicated that this PCG family is not linked to either of these two loci. Next a genome wide screening was initiated. Automated genotyping of 235 polymorphic markers identified only one marker (D14S53) with reduction in homozygosity in all PCG affected individuals as compared to the unaffected members. Saturation mapping and haplotype analysis with 6 additional markers: D14S61, D14S42, D14S983, D14S1020, D14S74 and D14S1000 found that all affected individuals share a region of homozygosity defined by markers D14S42, D14S983, D14S1020 and D14S74. All markers segregated perfectly with the disease phenotype. These data suggested that the third PCG locus (GLC3C) is located on chromosome 14q24.3 within a region of 2.9 cM that is flanked by markers D14S61 and D14S1000. By using a complete BAC contig that covers this area we were able to identify 7 known genes mapping within the GLC3C candidate region: Neurexin 3A, Nuclear Receptor ERRB2, KIAA0759, Glutathione Transferase Zeta 1, Maleylacetoacetate Isomerase, Serine Palmitoyl Transferase Subunit II and Alk B protein Homologue. Conclusions: A genome-wide screen in a multigenerational consanguineous family with PCG indicates that the third PCG locus (GLC3C) resides on chromposome14q24.3 within a 2.9 cM region flanked by markers D14S61 and D14S1000. Supported by a NEI grant EY-11095 to MS.
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