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, retinitis pigmentosa, and Leber congenital amaurosis. METHODS After isolation of human genomic clones, the structure of IMPG2 was determined by sequence analysis. Mutational analyses were conducted on genomic DNA isolated from 316 probands using single-strand conformation polymorphism analysis. RESULTS The IMPG2 gene is organized into 19 exons, and the structure of the gene is highly similar to that of the IMPG1 gene, which encodes another retinal proteoglycan, IPM 150. Mutational analyses indicate that the observed sequence changes are present at approximately equal rates in donors with and without retinal disease. Additional data derived from RT-PCR and Northern blot analysis show that IMPG2 is processed in the human retina into multiple alternatively sized transcripts that may represent splicing isoforms. CONCLUSIONS Analysis of the overall relationship of human IMPG2 (located on chromosome 3q12.2-12.3) to human IMPG1 (located on chromosome 6q14) suggests that these genes have evolved from a common ancestral gene. Although this is an excellent candidate gene for hereditary retinopathies, single-strand conformation polymorphism analyses provided no evidence that variations in IMPG2 coding region are responsible for the inherited retinopathies examined.