COPROPORPHYRINOGENE OXIDASE - GENE ORGANIZATION AND DESCRIPTION OF A MUTATION LEADING TO EXON-6 SKIPPING

Genomic clones containing a human copropouphyrinogen oxidase gene, wer e isolated. DNA sequencing indicates that the human CPX gene spans abo ut 14 kb and consists of seven exons and six introns. Sequences were d etermined for all the exons, exon-intron junctions and for 800 bp of p romoter region. Introns vary in size from 269 bp to 5 kb and they all have consensus sequences at their boundaries. Primer extension and rib onuclease protection experiments revealed multiple transcriptional ini tiation sites in a region with sequence motifs characteristic of a pro moter. The promoter region is CC-rich and contains multiple potential Spl elements, CACCC boxes and potential GATA-1 binding sites. The avai lability of the CPX genomic sequence allowed us to determine the mutat ion in a patient with a hereditary coproporphyria. A G to A mutation w as found at the last position of exon 6. This mutation results in exon skipping.