Genomic organization of human DLG4, the gene encoding postsynaptic density 95

We have determined the exon-intron organization and characterized the 5'-flanking promoter region of DLG4. Encompassing approximately 30 kb, the DLG4 locus is composed of 22 exons that range in size from 28 to 1,218 nucleotides. All splice sites conform to the GT-AG rule, 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 these 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. Analysis of the core promoter region for DLG4 suggests that the expression of this gene is controlled by a TATA-less promoter using a single transcriptional start site embedded within a CpG island. DLG4 maps to a region on chromosome 17p13.1 known to contain a locus for autosomal dominant cone dystrophy 5. Scanning for mutations in the DLG4 coding region and splice sites was performed in 15 cone dystrophy patients, including probands from five families showing linkage to the DLG4 region. No disease-causing mutations were identified in any patients, suggesting that DLG4 is not the causative gene for this genetic eye disorder.