Molecular characterization of a ferrochelatase gene defect causing anomalous RNA splicing in erythropoietic protoporphyria.

Erythropoietic protoporphyria is an inherited disorder caused by deficient activity of the enzyme ferrochelatase. We have examined the ferrochelatase gene in an 11-year-old female with protoporphyria and have found that she is heterozygous for a mutation at a conserved residue in the exon 3 donor splice site consensus sequence (T(+2)-->G). This is inherited from her father, who also has deficient ferrochelatase activity. As a consequence of the mutation, ferrochelatase transcripts are aberrantly spliced and give rise to mRNA molecules in which sequences corresponding to exon 3 are absent. This leads to the expression of a ferrochelatase protein lacking a central region of 40 amino acids.