Molecular characterization of a novel defect occurring de novo associated with erythropoietic protoporphyria

A ferrochelatase (FC) mRNA lacking exon 4 was detected in a patient with erythropoietic protoporphyria (EPP). The mutation responsible for the exon skipping was a novel one: a G-->C transition at the -1 position of the exon 4 donor site (nucleotide 463). The efficiency of missplicing was not 100%. The same mutation could alternatively result in exon 4 skipping or act as a missense mutation (G463-->C, predicting an Ala155-->Pro substitution), that inactivates the FC activity almost completely. Both parents were negative for the mutation and DNA fingerprinting indicated that both of them are the biological parents with 99.58% certainty. This is the first report of a de novo mutation in EPP.