A novel splicing mutation in the ferrochelatase gene responsible for erythropoietic protoporphyria.

An aberrant ferrochelatase mRNA lacking exon 7 was found in a patient with erythropoietic protoporphyria (EPP). The exon 7 skipping appears to result from a G >> A transition at position +5 of the donor site of intron 7 of the ferrochelatase gene. The patient is heterozygous for the mutation. Since the patient's paternal half-brother (not available for testing) also has clinically obvious EPP, their father appeared to be the source of the mutant allele. The father was in fact found to be a carrier of the same mutation and his ferrochelatase activity was 35% of normal; however, he is asymptomatic, with only a slightly elevated erythrocyte protoporphyrin level. These findings confirm that the observed mutation is responsible for the defect. The variability in clinical expression of EPP probably reflects the great heterogeneity of the ferrochelatase gene defects and the contribution of additional exogenous and endogenous inducers of latent disease.