Research on the epigenetics and environmental factors in erythropoietlc protoporphyria

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We investigated the presence of mutations of ferrochelatase (FECH) gene in 5 unrelated Japanese erythropoietic protoporphyria (EPP) patients who developed acute hepatic failure. Genomic DNA extracted from peripheral blood leukocytes, was examined by amplifying each exon of the FECH gene and performing single strand conformation polymorphism (SSCP) analysis, followed by direct-sequencing to look for mutations. Molecular analysis, was also applied for the pedigree analyses.A total of 4 unique mutations were identified in 5 unrelated Japanese patients. Each mutation encodes truncated protein, and the activity of the FECH expressed in a E.coli expression system was decreased compared to the normal control. These mutations changed cleavage sites of the specific restriction enzyme or showed specific SSCP patterns, and could be screened by an amplified fragment from genomic DNA by the specific enzymes or specific SSCP patterns.This study adds some new mutations to those that have been previously reported together with a concurrent and additional cause of liver failure. However, we could not exactly elucidate the reason of liver complications, because there are asymptomatic carriers in their families who showed the same mutations but never develop hepatic disorder. We are now trying to analyze the other normal allele, so-called メ low expressed モ wild-type FECH allele.