A NOVEL MUTATION IN THE FERROCHELATASE GENE ASSOCIATED WITH ERYTHROPOIETIC PROTOPORPHYRIA

Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by mutations of the ferrochelatase gene, We investigated a Japanese pati ent with a dominant form of erythropoietic protoporphyria for a ferroc helatase mutation. Sequence analysis of the proband's ferrochelatase c DNA revealed a T to C point mutation at nucleotide 557. This mutation resulted in the replacement of Ile by Thr at amino acid position 186. a novel mutation in erythropoietic protoporphyria. An increase in ferr ochelatase activity was not observed in the crude extract of E. coli o ver-expressing the mutant protein compared with the control, whereas a marked increase in activity was observed in that overexpressing the w ild type. Prediction of the secondary structure of ferrochelatase sugg ested that the Ile(186) --> Thr mutation changed the original beta-she et structure to an ct helix in the region including amino acid residue of mutation, We conclude that, in this patient, the Ile(186) --> Thr mutation had abolished enzyme activity, possibly by disrupting the sec ondary structure, thereby causing erythropoietic protoporphyria.