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 i ntron 7 of the ferrochelatase gene. The patient is heterozygous for th e mutation. Since the patient's paternal half-brother (not available f or 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 elevate d erythrocyte protoporphyrin level. These findings confirm that the ob served mutation is responsible for the defect. The variability in clin ical expression of EPP probably reflects the great heterogeneity of th e ferrochelatase gene defects and the contribution of additional exoge nous and endogenous inducers of latent disease.