COMPLEX PATTERN OF ALTERNATIVE SPLICING IN THE NORMAL UROPORPHYRINOGEN DECARBOXYLASE GENE - IMPLICATIONS FOR DIAGNOSIS OF FAMILIAL PORPHYRIA-CUTANEA-TARDA

We describe multiple alternative transcripts of uroporphyrinogen decar boxylase mRNA in normal individuals and patients with familial porphyr ia cutanea tarda. mRNA was reverse-transcribed, subjected to the polym erase chain reaction, and analyzed for nucleotide sequence. Seven diff erent transcripts were characterized, and a cryptic splice acceptor si te was identified in intron 1. In all mRNAs the exons abutted at previ ously defined exon boundaries. Characterization of the splice junction s in the genomic DNA showed that splice donor and acceptor sequences c omplied with the consensus sequences for these sites except for the sp lice acceptor sequences of exons 3 and 10. These deviations were prese nt in two normal individuals and one patient with familial porphyria c utanea tarda and were thus unable to explain the multiple aberrant uro porphyrinogen decarboxylase transcripts. We conclude that apparent del etions observed in transcripts derived from the uroporphyrinogen decar boxylase gene in patients with familial porphyria cutanea tarda should be interpreted with caution.