Genomic organization of human DLG4, the gene encoding postsynaptic density95

We have determined the exon-intron organization and characterized the 5'-fl anking promoter region of DLG4, Encompassing similar to 30 kb, the DLG4 loc us is composed of 22 exons that range in size from 28 to 1,218 nucleotides. All splice sites conform to the GT-AG Yule, except for the splice acceptor site of intron 5, which is TG instead of AG. Three different exons of DLG4 were found to be alternatively spliced in a subset of tissues. Two of thes e variants result in altered postsynaptic density 95 (PSD95) isoforms that dramatically truncate the protein. The third splicing variant represents an extension of exon 4 that encodes an additional 33-amino acid segment. Anal ysis of the core promoter region for DLG4 suggests that the expression of t his gene is controlled by a TATA-less promoter using a single transcription al start site embedded within a CpG island. DLG4 maps to a region on chromo some 17p13.1 known to contain a locus for autosomal dominant cane dystrophy 5. Scanning for mutations in the DLG4 coding region and splice sites was p erformed in 15 cone dystrophy patients, including probands from five famili es showing linkage to the DLG4 region. No disease-causing mutations were id entified in any patients, suggesting that DLG4 is not the causative gene fo r this genetic eye disorder.