Organization of the human IMPG2 gene and its evaluation as a candidate gene in age-related macular degeneration and other retinal degenerative disorders

PURPOSE. To characterize the genomic organization of human IMPG2, the gene encoding the retinal interphotoreceptor matrix (IPM) proteoglycan IPM 200, to evaluate its relationship to IPM 150, and to evaluate its involvement in inherited retinopathies, such as age-related macular degeneration, retinit is pigmentosa, and Leber congenital amaurosis. METHODs. After isolation of human genomic clones, the structure of IMPG2 wa s determined by sequence analysis. Mutational analyses were conducted on ge nomic DNA isolated from 316 probands using single-strand conformation polym orphism analysis. RESULTS. The IMPG2 gene is organized into 19 exons, and the structure of th e gene is highly similar to that of the IMPG1 gene, which encodes another r etinal proteoglycan, IPM 150. Mutational analyses indicate that the observe d sequence changes are pre sent at approximately equal rates in donors with and without retinal disease. Additional data derived from RT-PCR and North ern blot analysis show that -IMPG.2 is processed in the human retina into m ultiple alternatively sized transcripts that may represent splicing isoform s. CONCLUSIONS. Analysis of the overall relationship of human IMPG2 (located o n chromosome 3q12.2-12.3) to human IMPG1 (located on chromosome 6q14) sugge sts that these genes have evolved from a common ancestral gene. Although th is is an excellent candidate gene for hereditary retinopathies, single-stra nd conformation polymorphism analyses provided no evidence that variations in IMPG2 coding region are responsible for the inherited retinopathies exam ined.