Genetic analysis of the ferrochelatase gene in eight Japanese patients from seven families with erythropoietic protoporphyria

ABSTRACT A decrease in the activity of ferrochelatase (FECH; EC 4.99.1.1), the terminal enzyme of the heme biosynthetic pathway, results in erythropoietic protoporphyria (EPP; MIM 177000). We analyzed the FECHgene in eight Japanese EPP patients from seven non‐consanguineous families and found two distinct genomic DNA abnormalities. In six patients from five families, there was a G‐to‐A point‐mutation at the first position of the intron 9 donor site; it resulted in aberrant splicing and skipping of exon 9 in FECH mRNA. In one patient, we found an A‐to‐G point‐mutation 4 bases from the 3" terminus of intron 4 that led to the in‐frame insertion of 3 bases in mRNA. No allelic anomalies, except for 3 single nucleotide polymorphisms were detected in another patient. We analyzed intron polymorphism at IVS3‐48, known to be associated with the phenotypic expression of EPP, in these eight patients and 152 healthy Japanese volunteers. All patients were C/C homozygous for IVS3‐48. The allelic frequency of IVS3‐48C polymorphism in the healthy Japanese volunteers was 67.8% (103/152).